Discovery of Natural Product Anticancer Agents

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Investigations on the etiology of cancer in the hudson river tomcod population

The prevalence of tumors was compared between tomcod from the HR and the cleaner Sheep-scot River, Maine, that were collected in June as juveniles and reared under controlled laboratory conditions to December (spawning time) of that year (Cormier and Racine, 1990). This study was based on the assumption that early life stages in fish are most sensitive to the carcinogenic effects of contaminants and that critical exposures to cancer-causing contaminants had occurred by June in the environment. In December, tumors and other hepatic lesions were absent in tomcod from both populations and therefore no insights were gained into the etiology of neoplasia. These results were consistent with almost all other attempts to induce tumors under controlled laboratory conditions in fishfromnaturalpopulations that exhibit epizootic episodes of neoplasia and suggested that other approaches were needed to identify the cause of disease.

Table 1181 Criteria For Evaluating Carcinogen Experiments On Animals

Two species of rats, and both sexes of each adequate controls sufficient animals to resolve any carcinogenic effect treatment and observation throughout animal lifetimes at range of doses likely to yield maximum cancer rates detailed pathological examination statistical analyses of results for significance beyond the level of cancer in the control group Were tumors found remote from the site of administration No tumors observed should Refer to NCI's Guidelines for Carcinogen in Small Rodents

Testing for Carcinogenicity and Teratogenicity

Carcinogenic potential can be detected by three types of tests long-term carcinogenicity studies, rapid screening tests, and biomarkers. Long-term tests are the most definitive. These generally use mice or rats and last the lifetime of the animals (18 and 24 months, respectively). Two or three dose levels are usually used, the highest being the maximum tolerated dose'' (MTD). The MTD is estimated from 90-day studies and is chosen so as not to produce severe noncarcinogenic toxicological effects or to reduce significantly the life of any organisms that do not develop tumors. The other doses are typically one-fourth to one-half of the MTD. The number of tumors is recorded by animal (location, whether benign or malignant, the presence of any unusual tumors), the number of animals with tumors, the number of tumors per animal, the number of tumor sites, and the time to onset. In the United States, a set of minimum test standards for carcinogenicity has been developed by the National...


Cancer is possibly the most dreaded toxic event and probably the hardest for which to provide reassuring safety precautions (Williams and Burson, 1985). Normal cells respond to the presence of adjacent cells by ceasing to replicate. In cancer, the mechanisms limiting the growth of cells become damaged. The damaged cells grow uncontrollably, forming tissue masses called tumors (except in some cases, such as leukemia, the cancer of the white blood cells). This growth consumes the resources of the organism impinges on nearby tissues, causing them to atrophy and ultimately results in mortality. A great amount is understood about the causes and progresson of cancer, yet we are still far from having a complete understanding, or even from knowing enough to treat the disease effectively. The Stages of Cancer Cancer progresses in distinct stages. The first step, which produces no symptoms, is a first mutation that predisposes the cell to cancer. This step is called initiation. In the second...

Kenneth H Mayer and HF Pizer

Infectious disease is one of the great tragedies of Jiving things - the struggle for existence between different forms of life. Man sees it from his own prejudiced point of view but clams, oysters, insects, fish, flowers, tobacco, potatoes, tomatoes, fruit, shrubs, trees, have their own varieties of smallpox, measles, cancer, or tuberculosis. Incessantly, the pitiless war goes on, without quarter or armistice - a nationalism of species against species The important point is that infectious disease is merely a disagreeable instance of a widely prevalent tendency of all living creatures to save themselves the bother of building, by their own efforts, the things they require. Whenever they find it possible to take advantage of the constructive labors of others, this is the direction of the least resistance About the only genuine sporting proposition that remains unimpaired by the relentless domestication of a once free-living human species is the war against these ferocious littie fellow...

A tribute to John Stuart Gray 19412007

The marine science community was greatly saddened to learn of the death of Professor John Gray PhD DSc on Sunday 21 October 2007 at the age of 66 following a battle with pancreatic cancer. John was an internationally renowned environmental scientist whose research was dedicated to moving benthic ecology and studies of marine pollution from observation to hypothesis testing and finally, in a natural progression, to practical, applied usage of monitoring techniques. John was also a dedicated educator, not only of undergraduate and postgraduate students in Norway and abroad but also of governments and the general public, and his intellectual contributions will undoubtedly continue to shape the future of marine benthic ecology, marine pollution studies and their various applications. Above all, John was a wonderful friend, colleague, mentor, and gentleman (in all senses of the word) and will be greatly missed.

Past and Current Crimes

Before we concentrate on the chemical aspects of pollution, it is worth remembering that this is not the only form of pollution. Noise is an example of physical pollution. Simply adding water to a river at a different temperature to the ambient can effect life in the river. This is a form of thermal pollution. Pollution is, however, often associated with the introduction of chemical compounds into the environment. Popular opinion usually sees these as unnatural (and therefore harmful) substances. Perhaps one of the best known recent examples was the concern over the emission of chlorofluorocarbons (CFCs). These have been used in aerosol sprays and other applications. They are linked with the depletion of ozone in the stratosphere, which could lead to an increase in the intensity of harmful ultraviolet radiation from the sun reaching the earth's surface and increasing the incidence of skin cancer. Although the production of CFCs themselves is now banned in developed countries, the...

Detection And Purification Of Biochemical Compounds

Immunoassay uses antibodies to form a precipitate with specific compounds. Antibodies are special proteins produced by the body to bind with foreign substances so that they can be made harmless. Each antibody is highly specific, binding only to a single substance and binding extremely tightly in what is called a lock-and-key relationship. Molecular biology techniques have enabled the production of large quantities of antibodies of a specific type, called monoclonal antibodies. They are used for research purposes as well as to detect specific hormones in pregnancy tests and tests for prostate cancer. Immunoassay is a highly sensitive and selective detection method. Its use has been extended to organic pollutants and even to heavy metals.

Other evolutionary theories

And thereby fail to work (hence ageing arises as a consequence of damage to beneficial genes, rather than functioning genes that are actively deleterious). The theory is an attractive one, and may help explain the late-life plateau in mortality rates seen in many species87 (see also Fig. 1.3 for some evidence of a levelling effect in human cancer rates).

The emergence of Hivaids

It was within the epicenters of gay life - San Francisco, New York, and Los Angeles - that omens of an epidemic were first recognized. In 1980 and 1981, physicians in these cities began diagnosing rare conditions, Pneumocystis cari-nii pneumonia and Kaposi's Sarcoma (a skin cancer), in young homosexual men. The fact that these diseases were very rare, were being seen in an unexpected context, and were clustering in homosexual men hinted at the possibility of an emerging epidemic. The first published reports of the sudden outbreak of these conditions came from clinicians in these three cities who simultaneously noted that what they were observing might be related to a homosexual lifestyle (CDC, 1981a, 1981b). That several of the individuals represented in these reports had already died underscored the seriousness of this fledgling epidemic. Other unusual opportunistic infections were also showing up in gay men, prompting conjecture that a common underlying immune suppressing disease

Delineation of the Tropics

The tropics comprise that area of the world between the Tropic of Cancer (latitude 23.5 N) and the Tropic of Capricorn (latitude 23.5 S). These parallels mark the points that the sun reaches at its greatest declination north or south. Outside these latitudes, the annual amount of solar energy reaching the earth's surface generally decreases as a function of increasing latitude (Kondratyev 1969). From an ecological perspective, it is more useful to delineate the tropics on the basis of energy balance, as indicated by temperature, rather than latitude. One approach has been to use the mean annual 20 C

Genetic Engineering and Society

Suppose that a new variety of rice were developed by genetic engineering techniques that could be cultured in salt water, increasing arable land availability. Would it become a weed that will choke salt marshes around the world If a cancer gene were transfected into a common infectious virus, could it spread a new epidemic If a bacterium were engineered to biodegrade xenobiotic toxic pollutants or oil spills, would it spread to destroy chemicals in useful applications, or infect petroleum stocks Some of these risks can readily be discounted, although others remain. The possibility of bacterially transmitted cancer was taken seriously enough by biologists so that in the mid-1970s they agreed to a moratorium on recombinant DNA research until tests showed that transmission did not occur. Infection of oil wells would be limited not by the ability of bacteria to biodegrade oil, which they already are capable of, but rather by the limitations in that environment of water, oxygen, and...

Licit and illicit opium cultivation

A striking dichotomy of the nearly global criminalization of illicit opiate use is that opiates remain widely used in modern medicine and surgery, widely prescribed by physicians and other providers, and legally cultivated for these purposes. Drugs used in modern medicine and derived from the opium poppy include morphine, Demerol, codeine, and methadone, to name only a few (Physicians' Desk Reference, 2005). Anyone who has had major surgery, or the kind of severe pain associated with bone fractures, cancer, and dental emergencies, has likely known the extraordinary power of these agents to control human pain. They remain, for the most severe pains we suffer, the ultimate remedy - few of us who die in hospital will die without their benefit. But in their power lies their danger - as the Akha have told us. Opiates are highly addictive for humans precisely because the human nervous system is so richly endowed with opiate-like receptors - the famous endorphins, which were actually named...

Bruce A Wilcox Duane J Gubler and HF Pizer

Unfortunately, the major successes in controlling infectious diseases in the 1950s and 1960s was followed by two coincident global trends that would have an impact on the dramatic re-emergence of infectious diseases in the waning years of the twentieth century. The first was the redirection of the resources that were once used to control infectious diseases to other public health priorities, such as the War on Cancer in the early 1970s. The perception that infectious diseases were no longer a problem led to decreased resources, widespread deterioration of public health infrastructure to deal with infectious diseases, and complacency among government and public health officials as well as the public (Smolinski etal, 2003). This trend included medical education with a de-emphasis on preventive medicine and a strong focus on curative medicine in medical schools. Today, training in preventive medicine is not included in the curriculum of most medical schools in the US.

Endocrine System And Homeostasis

The nervous system is not the only way the body controls bodily functions. It also uses chemical messengers. Some cells communicate directly with their contact neighbors through special junctions. This is usually to coordinate local activity such as ciliary movement or muscle contractions. Others release chemicals into the intercellular spaces that primarily affect cells in the same tissue. An example is the prostaglandins, a powerful fatty acid with many functions. Prostaglandins are released by damaged tissues and stimulate inflammation and the sensation of pain. Aspirin and other analgesics act by inhibiting the formation of prostaglandins and similar compounds. Many tissues issue chemicals that inhibit cell division locally. This prevents uncontrolled growth such as occurs in cancer tumors. Compounds such as these are called local hormones or paracrine factors. Some specialized cells produce chemicals that are excreted through ducts onto epithelial surfaces, such as inside the...

Cytochrome P450Mediated Effects

Cancer promotion An association between dioxins and cancer has been recognized for some time, TCDD causing skin and liver tumors in mice at lower concentrations than any other substance. It is felt by some authorities that dioxins are not mutagenic (i.e., do not initiate cancer development), but it is generally felt that they are strong promoters of tumor development

Reproduction And Development

The reproductive system is the only system that is not essential to a person's survival. It is, however, essential to the survival of the species. Because cells replicate continually, they are subject to errors of replication, either due to the inborn rate of error or because of environmental agents such as chemical pollutants or radiation. This makes the reproductive organs susceptible to diseases associated with genetic damage. These range from cancer, which affects the individual, to birth defects and mutations, which affect a person's offspring. Some pollutants are thought to mimic the sex hormones, affecting reproduction and development.

Effects Of Isolated Glucosinolate Hydrolysis Products On Insects

Numerous studies have shown that glucosinolate hydrolysis products or extracts of glucosinolate-containing plants are toxic to a wide range of organisms besides insects, including bacteria, fungi, nematodes, and mammals.1'3'1924 Many of these investigations were motivated by concerns associated with the toxic effects of glucosinolate-containing animal feed and by the cancer-preventing activity of glucosinolate-containing vegetables in humans, as well as by the desire to use plant tissues as biopesticides. While these investigations bear testimony to the broad range of biological activities associated with glucosinolate hydrolysis products, due to the large volume of such reports, we limit the present review to studies that employed isolated glucosinolate hydrolysis products and that tested their effect on insects directly. However, we also include non-insect studies where the effects of different hydrolysis products of a single glucosinolate were compared.

Encounter competition See competition

Such endocrine-disrupting chemicals are thought to be involved in fertility problems in humans as well as other animals, and especially in fish and other aquatic organisms. They are also implicated in some cancers, such as breast and testicular cancer. Natural estrogens and synthetic estrogens used in hormone treatments and contraceptives are found in sewage effluent. Other endocrine disrupters include tributyl tin oxide, which causes female dog whelks to become masculinized, and certain industrial detergents, which cause male trout to produce vitel-logenin, an egg yolk protein normally produced only by females.

Studies with Laboratory Animals Effects of Endocrine Disrupting Chemicals in Plastic

Recent findings include chromosomal damage in developing oocytes in mouse ovaries, and abnormalities in the entire reproductive system in male mice, including a decrease in testicular sperm production and a decrease in fertility, In addition, fetal exposure to bisphenol A increases the rate of postnatal growth and decreases the age at which females mature sexually (go through puberty). These females also have mammary gland abnormalities, and mammary glands appear precancerous by the time the females reach young adulthood. Bisphenol A also causes abnormal brain development, and changes in brain function and behavior. Bisphenol A also disrupts immune function. Bisphenol A is also an animal carcinogen, since exposure to a very low dose during early postnatal development causes prostate cancer in rats.

Examples of Endocrine Disruption

Coincident with emerging knowledge of the ability of EDCs to disrupt a range of developmental processes, increases have been reported in a wide range of human health diseases and abnormalities, though some remain controversial. These include increases in the frequency of (obesity and cognitive behavioral dysfunctions, such as autism and attention deficit hyperactivity disorder (ADHD). There have also been increases in a cluster of male reproductive outcomes (cryptorchism, hypospadias, testicular cancer, and decreased sperm function) all of which are believed to originate in utero, and have been termed the testicular dysgenesis syndrome. . The strength of the epidemiological evidence demonstrating these epidemics varies. For example, there is little argument that there has been a widespread increase in rates of obesity and diabetes, but there is still significant debate about global decreases in reproductive function or increases in ADHD, due to limitations of historical data. While...

The Low Dose Issue and InvertedU Dose Response Relationships for EDCs

Developmental stages are typically far more vulnerable to signal disruption than adult stages. This is thought to occur for several reasons, including the absence of fully developed protective enzyme systems and higher metabolic rates. Most importantly, however, the events underway in development involve a series of organizational 'cross-roads' that are irreversible once the 'choice' in development is determined. In sharp contrast, in adults, the 'activational' processes at play can very often be reversed by removing the EDC, thus returning gene expression levels and organ function to normal. One recent example documenting extraordinary differential sensitivity of adult versus developing life stages was that adverse effects in tadpoles occurred at 1 30 000th of the lowest concentration of atrazine, a widely used herbicide, that was found to produce adverse effects in adults. Another related example from pharmacology is the synthetic estrogen diethylstilbestrol (DES), which caused...

Environmental resistance See biotic potential

Epidemiology The study of the incidence, distribution, and control of diseases affecting large numbers within a population. These include both epidemics of infectious diseases and diseases associated with environmental factors and dietary habits (e.g. lung cancer, some forms of heart disease, etc.).

Simulation of chemical reaction networks

The simulation of chemical reaction networks on SPICE has had significant applications. The methodology is rather simple (Wyatt 58 , Wyatt, Mikulecky and De Simone 59 ). The most extensive of these applications is in the area of biochemical pharmacological networks (Thakker, Wood, and Mikulecky 75 , Thakker and Mikulecky 76 , Walz, Caplan, Scriven, and Mikulecky 78 ). Let's look at an example from biology. This particular system, folate metabolism, is an important one in the synthesis of nucleic acids on the way to making building blocks for DNA and RNA. For that reason it plays an important role in cancer chemotherapy. (Seither, Trent, Mikulecky, Rape, and Goldman 71,72 , Seither, Hearne, Trent, Mikulecky, and Goldman 73 , White 79, 80 , White and Mikulecky 81 ).

Issues Concerning Assessing Risks Posed by EDCs to Human Health

What triggers an investigation between an EDC and a human health effect Traditional ('classical') epidemio-logical studies were often designed to investigate unusual patterns of human health outcomes. Perhaps the most dramatic of these was the investigation of diethylstilbestrol (DES) in response to a cluster of seven cases of a rare vaginal cancer (clear cell adeno-carcinoma) in young women. Similarly, an awareness of increasing rates of lung cancer triggered the first studies of smoking and lung cancer. Some epidemiological studies of EDCs have similar origins. Indeed, DES itself is a quintessential EDC, and current research into possible EDC involvement in breast cancer causation and fertility impairment have been provoked by observations of human trends. All else being equal, the ability of an epidemiological study to identify the cause of an adverse outcome decreases as the prevalence of the outcome and the number of causal factors increase. For example, the identification of DES...

Changes in food processing

As cardiovascular disease, hypertension, and cancer were found to be linked to diets high in saturated fat and sodium, health promotion efforts shifted dietary consumption patterns away from the traditional meat and potatoes to less red meat, more chicken and fish, and more fruits and raw vegetables. There is greater emphasis on minimally processed foods, along with lower fat content and less sodium - characteristics attributed to a heart healthy diet. While these alterations to food content may be helpful in reducing cardiovascular risk, they can modify the food matrix to be less inhibitory to pathogenic as well as spoilage organisms.

Carbon in Environmental Engineering and Science

It traditionally has been the organic carbon (along with pathogens) that was of the greatest concern in water pollution (Section 15.2.7), leading to the construction of wastewater treatment plants (Chapter 16) that focus on its removal. Management of wastewater treatment sludges often has stabilization of the organic material as a major objective. (Stabilization involves conversion of readily degradable materials to those that change only slowly see later in this subsection). Municipal solid waste management also must stabilize the organic material (e.g., by incineration or composting), or else deal with the consequences (e.g., attraction of vermin, settling, and leachate and gas production during landfilling). Similarly, with soil and groundwater contamination, it is often organic carbon that is the target of remediation. Undesirable tastes and odors in drinking water, and the formation of cancer-causing compounds during disinfection, are traceable to organic compounds present in the...

Summary And Future Direction Of Aquatic Toxicology

Mysid shrimp, Americamysis bahia sp.* Neomysis sp.* Holmesimysis sp.* Grass shrimp, Palaemonetes sp. Oysters, Crassostrea virginica* Commercial shrimp, Penaeus sp. Oceanic shrimp, Pandalus sp. Blue crab, Callinectes sapidus Cancer crab, Cancer sp. Mysid shrimp, Americamysis bahia sp. Neomysis sp. Holmesimysis sp. Commercial shrimp, Penaeus sp. Grass shrimp, Palaemonetes sp. Sand shrimp, Crangon sp. Blue crab, Callinectes sapidus Cancer crab, Cancer sp. Ridge-back prawn, Sicyonia ingentis

Vaccine development at the turn of the twentyfirst century

The development of vaccines which protect against infection with Human Papilloma Virus (HPV) types 16 and 18 can prevent cervical cancers associated with chronic infection by these serotypes. These vaccines have the potential to reduce the most common cause of cancer mortality among women worldwide. However, to realize the enormous promise of these new vaccines, two formidable challenges must be overcome adolescent girls must be immunized prior to the onset of sexual activity, and this vaccine must be made widely available throughout the world.

The Achilles Heel of Malaria

The synergy here lies in the hypothesis that changes in odour profile may be linked to VOCs present in parasite-infected blood that are different from uninfected blood and that these VOCs may be exchanged with the lung cavity at the alveolar interface. In line with the development of breathalyzers for ailments in the developed world (lung cancer, breast cancer, early detection of heart transplant rejection, tuberculosis) we quickly realized the importance of the availability of such devices for non-invasive and rapid screening of patients for malaria parasites. The advantages are numerous (Knols 2005). In particular, a biomarker for gametocyte carriage would give tremendous power of tackling the infectious reservoir with gametocidal drugs or selective protection of hosts when carrying infectious stages.

Effects on Fitness and Ecological Parameters

Organisms because they may affect organismal-level fitness components. This may be translated into effects on populations, and eventually communities and ecosystems. This is illustrated in Figure 8. First, because DNA damage and mutations can lead to cell death and cancer, this may affect survival. Because DNA damage enhances the rate of cell senescence, accumulation of unrepaired damage and mutations may affect longevity and population age structure. DNA damage and mutations have their greatest deleterious effect on rapidly dividing cells. Because gonadal germ cells are rapidly dividing, they are particularly susceptible to the effects of DNA damage and mutations. Growth may also be affected because of induced cell death, interference with DNA replication, or induced delay of cell division (DNA damage induces cell cycle delay, a phenomenon that halts the cell cycle to allow time for repair before DNA replication or mitosis). Immune cells, both mature white blood cells and white blood...

Discussion of Key Questions

As a result of this research, PCBs have been labeled probable human carcinogens by the EPA, and are also suspected of inducing developmental and learning disorders, impairing human immune systems, andcausinglowbirth weights. Production of these chemicals hasbeenbannedinternationally under terms of the United Nations' recent treaty on Persistent Organic Pollutants (see http www. To determine the safe level of PCB exposure for a human population, environmental epidemiologists first decide what level of risk is acceptable. The U.S. Food and Drug Administration (FDA) has set the acceptable PCB level in fish sold for human consumption in interstate commerce at 2 parts per million (ppm, or milligram PCB per kilogram of edible fish tissue on a wet weight basis). This guidance, now seventeen years old, was based on the average amount of fish consumed by the American public and the known PCB effects on humans at the time. Since the FDA guidance level was set, the average U.S. diet has changed...

Methods for Asbestos Analysis

Asbestos is a term used for any one of a group of fibrous silicate minerals. These materials possess good heat and electrical insulation properties and have found widespread use in industry. It has, however, become a major environmental hazard. Airborne fibres are capable of being trapped in the lungs. The respiratory disease, known as asbestosis, can result, as well as a number of forms of cancer.

Microarrays can indicate costs of immunity

Once activated, the immune response needs to be kept in check to avoid the deleterious effects on fitness. The costs of an activated (or overactive) immune system include reduced fecundity, hyper-sensitivity to infection, cancer, (auto)inflammatory diseases, or developmental defects (Zerofsky et al., 2005 Bischoff et al, 2006 Aggarwal and Silverman, 2008). Multiple negative regulators of the immunity pathways have been identified in Drosophila, including feedback loops, degrading agents of the triggering molecules of the immunity pathways, and possibly a repressosome that binds to the promoter regions of effector genes (reviewed in Aggarwal and Silverman, 2008).

Individual Variability

Several examples in humans will show that individuals of the same species can have large genetic differences in responses to toxins. Many Orientals are genetically predisposed to a more rapid metabolism of ethanol to acetalydehyde. Since it is the metabolite that is responsible for many of the symptoms of ethanol intoxication, these people react strongly to even small doses, becoming flushed and uncomfortable. Another example is in the inherited propensity that some people have toward specific cancers, such as retinoblastoma, or skin or colon cancer. These people have inherited one of the ''hits'' required to convert a normal cell into a cancerous one. In a third example, millions of persons throughout the world have red blood cells with defects in their respiration pathways, such as a deficiency in glucose-6-phosphate dehydrogenase. These cells are not efficient in maintaining glutathione, which protects against peroxide attacks. People with this type of problem are especially...

Effects on Particular Organs or Organ Systems

Mechanisms that impair the release of triglycerides to the blood. Carbon tetrachloride and ethanol are among the substances that can cause this. Necrosis is caused by carbon tetrachloride, which forms free radicals in the liver, as well as by other halogenated hydrocarbons. Cirrhosis is the formation of scar tissue in the liver. It is also caused by carbon tetrachloride, although ethanol is most commonly associated with this condition. Although there is evidence to the contrary, the effect of ethanol may be related to nutritional deficiency associated with alcoholism. Cholestasis is an inflammation of the ducts carrying bile or a decrease in bile flow by other mechanisms. There are many types of liver cancer, and many chemicals are known to cause cancer in laboratory animals. The role of chemicals in human liver cancer is less clear, except for the notable case of vinyl chloride, which is known as a potent cause of angiosarcoma. Skin and Eye The stratum corneum (see Section 9.1) is...

Mutagenicity and neoplasia

Also, one recent study examined cancer in beluga whales and concluded that PAHs were the likely cause. As noted by one author, several factors relating to PAH exposure and toxicity, such as specificity of response, dose-response relationships, experimental evidence, and others, strongly support the conclusion of PAH-induced neoplasia for fish from contaminated sites. This is one of the few examples where a specific (or group of) contaminant(s) can be associated with adverse effects in organisms collected in the field, which is likely applicable for other species.

Destruction from spacedanger from supernovae

During the 1970s, several scientists attempted to explain the demise of the dinosaurs, and many other organisms, at the end of the Cretaceous (65.5 million years ago) by the effects of a nearby supernova. The mechanism underlying the extinction-by-supernova idea is that cosmic rays generated by these exploding stars can generate nitrogen oxides in the Earth's atmosphere, which react with ozone (O3) to produce 'normal' molecular oxygen (O2).11,12 As is now well known from widespread concern about modern ozone depletion and polar ozone holes, the reduction in ozone high in the Earth's atmosphere can allow dangerous levels of ultraviolet light through to the Earth's surface.13 This can in turn lead to increased levels of cancer and genetic mutations, potentially causing high rates of mortality.

Mechanistic Doseresponse Models

These models developed from hit theory explanations for carcinogenesis, and cancer remains their most important application. The one-hit model (originally developed for radiation effects) fits the assumption that a single reaction event can transform a cell to However, the one-hit model did not fit data well. A multihit model improved this situation. It assumed that several hits were necessary for a toxic effect, all of which had the same probability. This led to the multistage model, to fit the theory of carcinogenesis, which requires several hits to the same cell, each having different probabilities, to produce a malignancy The parameter k is the number of stages. Although evidence may indicate many stages (e.g., five stages in the case of colon cancer described above), for statistical validity at least k + 1 different dosage levels must be tested to determine k coefficients. It is often cost prohibitive to have so many levels. Note that dosage in these models is not...

Summary and Conclusions

In conclusion, the health effects that have resulted from exposures received as a result of nuclear weapons tests include thyroid disease exposed to 131I (iodine-131, t1 2 8 days) which concentrates in the thyroid gland as well as leukemia and solid cancers from low-dose rates of external and internal exposure. An obvious example is the 1945 atomic bombings of Hiroshima and Nagasaki in Japan more than 60 years ago. The bombings were tragic experiences for the cities and for many survivors who sustained severe radiation exposures and injuries from the blasted air shock waves. Radiation-associated deaths from leukemia (46 of all leukemia deaths) peaked within 10 years of the bombings. Many of these radiation-related cancer deaths continue to occur. It is a lifetime of suffering to the survivors. The Chernobyl accident produced similar results. To date, the United Nations reports that 4000 people developed thyroid cancer following that accident, and 56 people, mostly rescue workers, have...

Nonadditive Interactions

Ethanol and carbon tetrachloride have a synergistic effect on the liver, and tobacco smoke and asbestos interact in lung cancer. In the latter case the interaction was defined differently from that above. It was observed that asbestos workers who did not smoke experienced a fivefold increase in their risk of lung cancer, and cigarette smokers who did not work with asbestos had an 11-fold increase. However, asbestos workers who smoked experienced a 55-fold increase in lung cancer rate. Thus, the interaction here is defined in terms of additivity of risk instead of additivity of toxicity. An example of poten-tiation is isopropanol, which does not harm the liver by itself but greatly increases the toxicity of carbon tetrachloride. By reacting to form a more toxic substance (e.g., nitrites and some amines react in the stomach to form carcinogenic nitrosomines)

Ozone and ultraviolet effects

As well as worries about the addition of CO2 to the atmosphere, scientists are also concerned about the depletion of another gas, ozone. Ozone in the stratosphere absorbs much of the ultraviolet (UV) radiation from the sun. This is important because ultraviolet-B (UV-B) is harmful to most life forms. It is the UV-B rays from the sun that cause sunburn and skin cancer in humans and UV light is used to kill bacteria in sewage treatment plants.

In Situ Measurement of Conventional Toxicity

Biochemical tests on organisms in their habitats that can indicate toxic effects are called biomarkers. Biomarkers are of particular interest for compounds that do not bioac-cumulate, and that are thus difficult to measure in tissues directly. Any of the biochemical effects described above could be used. Examples include activity of enzymes such as cytochrome P450 (a positive indicator of toxicity) or acetylcholinesterase (a negative indication). Increased metallothionein is a sensitive biomarker for metal exposure. Despite their potential, they have not been widely found useful in environmental applications. Some have proven useful in clinical application for cancer detection.

Mutagenicity Testing and In Vitro Tests

A variety of mutagenicity tests has been developed. They can be categorized as tests that detect gene mutations, chromosome effects, DNA repair and recombination, or others. The others include tests for transformation of mammalian cells into malignant cancer cells in vitro. (The developer of this test, Bruce Ames, is an outspoken critic of the way that tests are used to identify carcinogens. He states The effort to eliminate synthetic pesticides because of unsubstantiated fears about residues in food will make fruits and vegetables more expensive, decrease consumption, and thus increase cancer rates. The levels of synthetic pesticide residues are trivial in comparison to natural chemicals, and thus their potential for cancer causation is extremely low.'')

Hazard Identification

Ecological hazards might result in fish kills, habitat destruction, or other environmental effects. If a potential hazard is identified, three other analyses become important for the overall risk assessment. Chemical toxicities are categorized according to the various health effects resulting from exposure. The health effects, often referred to as endpoints, are classified as acute (short-term) and chronic (long-term). Acute toxic effects occur over a short period of time (from seconds to days), for example skin burns from strong acids and poisonings from cyanide. Chronic toxic effects last longer and develop over a much longer period of time, and include cancer, birth defects, genetic damage, and degenerative illnesses. Carcinogens (Sittig 1985) Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs) American Conference of Governmental Industrial Hygienists (ACGIH 1990) Integrated Risk...

Extrapolation from Animals to Humans

Differences in the toxicity of specific substances between humans and laboratory animals cause considerable uncertainty in the application of animal data to humans. The differences can sometimes be isolated to differences in absorption, distribution, biotransformation, and excretion. For example, 2-naphthalamine is converted to the carcinogen 2-naphthyl hydroxylamine by dogs and humans. This is excreted by the kidneys and causes bladder cancer. However rats, rabbits, and guinea pigs do not excrete this metabolite and do not get bladder cancer from the original compound. Ethylene glycol is metabolized by two pathways with the separate end products oxalic acid or CO2. Cats metabolize more of the ethylene glycol to oxalic acid, whereas rabbits produce more CO2. Consequently, ethylene glycol is more toxic to cats than to rabbits. The LD50 for dioxin (TCDD) is 5 mg kg in hamsters but only 0.001 mg kg in guinea pigs. This large range in toxicity between species has produced considerable...

Table 1182 Factors Influencing Human Response To Toxic Compounds

Similar to immunological status could be a factor in cancer recurrence Interferes or facilitates absorption into the body Compounds absorbed on particulates may be retained at higher rate Synergisms, antagonisms, cancer promoters, enhanced absorption Temperature, humidity, barometric pressure, and season enhance absorption

Chemical Contamination

Chemical contaminants accumulate in salt marshes that receive surface-water runoff and or direct discharges of waste materials. Among the most toxic are halogenated hydrocarbons, which include many insecticides, herbicides, and industrial chemicals. When accumulated in the tissues of salt marsh animals a wide range of disorders can result, for example, immunosuppression, reproductive abnormalities, and cancer. Petroleum hydrocarbons pollute harbors and remnant salt marshes following oil spills, urban runoff, and influxes of industrial effluent and municipal waste. Once they move into anoxic sediments, they can persist for decades, reducing primary production, altering benthic food webs, and accumulating in bird tissues. Polycyclic aromatic hydrocarbons have additional carcinogenic and muta-genic potential for aquatic organisms.

Systematic random sampling See sampling

Temperate deciduous forest A major biome found in the mid-latitudes (temperate zone) between the Tropics of Cancer and Capricorn and extending to the Arctic and Antarctic Circles. Temperate deciduous forests have moderate climates with abundant and fairly evenly distributed rainfall. There is a marked seasonal change. The trees are shorter than those of boreal forest and are dominated by broad-leaved trees (oak, beech, lime, birch, hazel), which shed their leaves in the fall, an adaptation to lack of available water in winter. Many of these forests contain several different species of trees and are termed mixed deciduous forest. Warm temperate forests occur in south China, for example, and cool temperate rainforests also exist, in New Zealand, for example. In temperate deciduous forests there is a shrub layer beneath the canopy and a rich

Context Of Rational Action

Despite the anomalous time lag, the connection that Winterhalder and Goland (1997) make between the initial use and eventual domestication of important crops is surely cogent, but perhaps more akin to the stochastic connection between smoking and lung cancer. Smoking one cigarette will (probably) not produce cancer even a lifetime usually does not but surely the longer one smokes, the greater the chance. Fortunately, the tobacco company subterfuge that no precise connection between smoking and lung cancer has ever been shown, that most lifetime smokers never develop cancer, and so on, has been unsuccessful. The public is not misled they know that smoking causes lung cancer. It seems similarly pointless to deny that there is a connection between the conditions that promote the use of potential domesticates and their eventual domestication. Foraging theory provides an elegant account of some of those conditions.

Resistance of hudson river tomcod to pcbs and tcdd induced early lifestage toxicity

In summary, tomcod from the HR exhibit biomarker alterations at a variety of mechanistically linked hierarchical steps of biological organization from exposure through the community levels (Fig. 30.4). This is suggestive of a chemical etiology to cancer and perhaps reduced size of the HR population.

Medical and Laboratory Facilities

Radioisotopes are used extensively in medical facilities, biomedical research laboratories, and to a lesser extent in other types of laboratories (Table 11.22.2). Clinical use of radioisotopes is expanding rapidly in such areas as cancer treatment and diagnostic testing. The lack of waste management plans at many of these facilities results in frequent misclassification of materials as radioactive (Party & Gershey 1989). Relatively large amounts of radioisotopes are used in clinical procedures. Although most of these isotopes are strong emitters of gamma radiation, they have short half lives (Table 11.22.3).

Management Implications

Toxic responses that are meaningful at the organismic population community levels are only beginning to be evaluated in HR taxa. For example, despite their exposure to and bioaccumulation of cancer-causing toxicants, high prevalence of liver neoplasms, and a truncated age structure, laboratory studies have yet to be conducted in which the role of specific contaminants such as PCBs in inducing tumors is investigated in Atlantic tom-cod. Early life-stage toxicities are very sensitive and population-relevant outcomes in fish from exposures to PCDD Fs and coplanar PCBs. The likelihood of these compounds in eliciting these early life-stage effects in HR fish is only beginning to be explored. Similarly, fish are highly sensitive to EDCs, yet only recently have studies been initiated to evaluate these responses in fish exposed to HR contaminants.

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Finally, some organisms may undergo a phenomenon known as adaptive mutagenesis. In this process, environmental stressors cause an increase in endogenous or spontaneous mutations, presumably by endogenous inhibition of repair and mismatch detection. This is thought to be an adaptive mechanism whereby bacteria create de novo genetic variation, because some of the new variants may survive the stress better than others. It is not known if adaptive mutation occurs in eukaryotes, or genotoxic stressors can also induce adaptive mutations. However, a similar process occurs in cancer cells, which gradually accumulate more and more mutations after initiation of the tumor - a process called genomic instability. Latent genomic instability can also occur in radiation-exposed cells, which may spontaneously develop high numbers of mutations long after radiation exposure and initial repair of the damage to DNA.

Halogenated Aliphatic Hydrocarbons

Drug against cancer Treatment of leukemia and related cancer C, human carcinogen AC, animal carcinogen SC, suspected human carcinogen, PTP, USEPA's toxicity priority pollutant HW, hazardous waste (USEPA). C, human carcinogen AC, animal carcinogen SC, suspected human carcinogen, PTP, USEPA's toxicity priority pollutant HW, hazardous waste (USEPA).

Uptake and Metabolism of Benzene

P450 Catechol Oxidation

Although benzene is classified as a known carcinogen, it is generally thought to require metabolic activation by mixed function oxidases to form one of several DNA damaging nucleophiles. Experiments have shown that 'knockout mice' deficient in the cytochrome P450 2E1 enzyme (CYP2E1) are resistant to the carcinogenic effects of benzene, verifying the requirement for metabolic activation. The predominant benzene metabolite is benzene oxide, a very reactive epoxide which can rearrange nonenzymatically to form phenol (Figure 1). Phenol is the predominant urinary metabolite of benzene in mammals and is a known hematotoxin. Alternatively, benzene oxide can be further acted upon by CYP2E1 to form benzene oxepin (Figure 1), which can undergo iron-catalyzed ring opening to form reactive trans,trans-muconaldehyde. A third possibility involves epoxide hydratase action on benzene oxide to generate catechol (Figure 1 ). Phenol can be further acted upon by CYP2E1 to generate hydroxyquinone or...

Beyond the Traditional Ecological Risk Paradigm

Risks are quantified under the traditional ecological risk paradigm using the hazard quotient approach. A hazard quotient is defined as the ratio of an organism's estimated chemical exposure relative to a lowest-observed-effect level or a no-observed-effect level derived from laboratory toxicity testing or field data. The hazard quotient approach is rooted in human health risk assessment as a tool to measure the potential hazard (e.g., level of concern) posed by chemical exposure. As acknowledged by the US Environmental Protection Agency (EPA) in its Risk Assessment Guidance for Superfund (RAGS, Part A), a hazard quotient is in fact not a true measure of risk, but rather simply an indication of whether a threshold has been exceeded. This differs from EPA's approach toward carcinogenic risks to humans, which uses the linear low-dose cancer risk equation to estimate the probability of an individual's cancer risk over a lifetime. One proposed strength of the hazard quotient approach is...

Migration between the Hudson and New York Bight

Larval migration patterns documented for the Hudson River Estuary and New York Bight. 1) Estuarine retention eggs or larvae of two gastropods (periwinkle Littorina littorea, slipper shell Crepidula fornicata), one barnacle (Balanus improvisus), two mud crabs (Rhithropanopeus harrisii, Dyspanopeus sayi), spider crabs (Libinia spp.) and two fishes (bay anchovy Anchoa mitchilli, naked goby Gobiosoma bosc) were released in the estuary and larvae primarily remained there through development. 2) Estuarine-shelf migration larvae of three crab taxa (lady crab Ovalipes ocellatus, fiddler crabs Uca spp., blue crab Callinectes sapidus) were released in the estuary, emigrated to the shelf and returned to the estuary as postlarvae. 3) Shelf-estuarine migration bluefish (Pomatomus saltatrix) spawned on the shelf, larvae immigrated to the estuary and returned to the shelf as juveniles. 4) Shelf retention larvae of rock crabs Cancer spp. and eggs of five fish taxa (Gulf Stream flounder...

Risk Characterization

Risk is usually identified as a number. When the risk concern is cancer, the risk number represents the probability of additional cancer cases. For example, an estimate for pollutant X might be expressed as 1 X 10 or simply 10 6. This means one additional case of cancer projected in a population of one million people exposed to a certain level of Pollutant X over their lifetimes.

Losses in Stratospheric Ozone Layer

Several potential deleterious effects result from decreasing the stratospheric ozone concentration. Of major concern is increased skin cancer in humans resulting from greater UV radiation reaching the earth's surface. Additional potential concerns include the effects on some marine or aquatic organisms, damage to some crops, and alterations in the climate (Francis 1994). While environmental engineers are uncertain about all seasonal and geographic characteristics of the natural ozone layer and quantifying these effects, the effects are recognized via precursor pollutant control measures included in the 1990 CAAAs.

The Condition of the Waters

There seems to be some evidence that the residual chlorine from an upstream wastewater treatment plant can combine in the receiving waters with industrial wastes to form carcinogenic chlorinated hydrocarbons, which can enter the drinking water supplies downstream. Toxic chemicals from the water can be further concentrated through the food chain. Some believe that the gradual poisoning of the environment is responsible for cancer, AIDS, and other forms of immune deficiency and self-destructive diseases.

Table 514 Qualitative Summary Of The Effects Attributed To Specific Pollutants

Buildings aggravates lung illness Causes acute and chronic leaf injury attacks a wide variety of trees irritates upper respiratory tract destroys paint pigments erodes statuary corrodes metals ruins hosiery harms textiles disintegrates book pages and leather May be cancer-producing (carcinogenic) retards plant growth causes abnormal leaf and bud development

Lawn Chemical Use Ecology And Risk

Though the effects of 2,4-D, the most common of all yard herbicides, on human health are generally debated, expert panels have concluded that the weight of evidence supports the possibility that exposure can cause human cancers (Ibrahim et al. 1991). So too, neurotoxins like chlorpyrifos appear far more significant than has been generally accepted to date (Zartarian et al. 2000), and yard treatments have been shown to have strong associations with soft tissue sarcomas (Leiss and Savitz 1995). This is especially true for children pesticide usage, specifically including Diazanon as well as yard weed herbicides, has been shown to be associated with childhood brain cancer (Davis et al. 1993 Zahm and Ward 1998).

Mechanisms of Plutonium Toxicity

Depending on the exposure scenario, the resulting effects of the ionizing radiation include cytotoxicity and tissue necrosis (at higher doses) or genotoxicity (at lower doses), with cancer being the best documented in animal studies. In inhalation studies conducted with beagles, in order of frequency, bone, lung, and liver tumors were identified and determined to be the cause of death in many cases, with liver tumors being the least likely to result in death. The mechanisms of action for tumor development (and other non-tumor-forming mutations) are either direct radiation damage of DNA strands or indirect toxicity with strand damage after free radical generation. Other documented effects of plutonium exposure in (nonhuman) mammals include altered immune system structure and function, and reproductive effects.

Interaction between the local and systemic immune response

Nitric oxide (NO) is a signalling molecule implicated in multiple physiological processes in animals, including innate immunity. In vertebrates, NO possesses direct effector functions and is an important signalling molecule that regulates gene expression and influences cell differentiation. NO has also been implicated in gastrointestinal motil-ity, mucosal permeability after bacterial infection, and epithelial-associated pathologies such as colon cancer (Bogdan, 2001). In Drosophila, biochemical modulation of NO signalling has demonstrated its requirement in immune signalling between the gut and fat body. Reduction of nitric oxide syn-thase (NOS) activity in Drosophila using the inhibitor NG-nitro-L-arginine methyl ester (l-NAME), led to increased larval lethality after oral ingestion of Ecc15. In addition, this study demonstrated that exogenous NO in the gut triggers Diptericin expression in the fat body even in the absence of a pathogen (Nappi et al, 2000 Foley and O'Farrell, 2003)....

Nitrogen Export by Rivers

On the alleged links between high nitrate concentrations in drinking water and two health problems in humans the 'blue-baby' syndrome (methaemoglobinaemia) and gastric cancer. Now, there are also major concerns about environmental degradation. Nutrient enrichment in water bodies encourages the growth of aquatic plants (see Figure 5).

Hole in the Ozone Layer

In the stratosphere, twelve to sixteen km above the surface, ultraviolet light from the sun converts the oxygen molecule to ozone. Here, the conversion process creates an ozone layer that absorbs ultraviolet radiation, protecting the earth from most of its damaging rays. Ultraviolet radiation causes skin cancer, and it is associated with cataracts in eyes, gene mutations, and immune system damage. Ozone also inhibits photosynthesis in plants.

Contaminant Sources And Effects

Petroleum and individual PAHs from anthropogenic sources are found throughout the world in all components of ecosystems. Chapter 14 (Albers) discusses sources and effects of petroleum in the environment. Less than half of the petroleum in the environment originates from spills and discharges associated with petroleum transportation most comes from industrial, municipal, and household discharges, motorized vehicles, and natural oil seeps. Recovery from the effects of oil spills requires up to 5 years for many wetland plants. Sublethal effects of oil and PAHs on sensitive larval and early juvenile stages of fish, embryotoxic effects through direct exposure of bird eggs, and acute effects in vertebrates are discussed. Evidence linking environmental concentrations of PAHs to induction of cancer in wild animals is strongest for fish. Although concentrations of individual PAHs in aquatic environments are usually much lower than concentrations that are acutely toxic to aquatic organisms,...

Hydrocarbons Solvents Pahs And Similar Compounds

The major toxic effects common to these compounds are CNS depression, including narcosis, and irritation. These are of special concern with acute exposure to the solvents. However, these types of compounds can cause other effects, ranging from liver or kidney damage to carcinogenesis. CNS depression is essentially the action of a general anaesthetic. The potency of organics to produce CNS depression increases with the chain length of the compound. Halogenation, addition of an alcohol group, or unsaturation (removal of hydrogen to form a double carbon-carbon bond) increase potency as well. Alcohols, including glycols, are much stronger CNS depressants than aliphatics are and slightly more irritating. As carbon chain length increases, irritation decreases but lipophi-licity increases, as does systemic toxicity. Methanol is less inebriating than ethanol but has the unusual property of destroying the optic nerve. Fifteen milliliters can cause blindness. As with ethanol, it is metabolized...

About the Editors

Miscarriage (Coping With A Miscarriage, with Christine O'Brien Palinski, The Dial Press, 1980), and artificial insemination (Having a Baby Without A Man, with Susan Robinson, MD, Simon & Schuster, 1985). He also co-authored Confronting Breast Cancer (with Sigmund Weitzman and Irene Kuter, Random House, 1987). From 1984 to 1994 he was founder and President of New England Medical Claims Analysts, a health-care consultancy, and during that time wrote and lectured on health-care cost containment. Presently he is Co-founder and Principal of Health Care Strategies, a consulting firm in Cambridge, Massachusetts, that provides program evaluation and management consulting services to community health-care providers, health-care systems, and social service organizations. Health Care Strategies specializes in working with clients to help them design and implement low-cost, practical systems for program evaluation. The goal is for providers and community-based organizations to be able to...

Biographical sketch

David Graham Lloyd was born on June 20,1937 at Manaia, Taranaki on the North Island of New Zealand, with his identical twin brother Peter Lloyd (Fig. 1.1a). Apparently, the twins were so similar that only their mother could tell them apart reliably. Unfortunately, she died of cancer when they were eight leaving their father, a dairy farmer at Taranaki, to raise the twins, their brother Trevor and sister Judith. We are particularly indebted to Peter and Trevor Lloyd for providing many of the details for this biographical sketch of David Lloyd.

Surface currents

The chief surface currents and their relation to prevailing winds are shown in Figure 1.6. In the Equatorial belt between the Tropics of Cancer and Capricorn, the North-East and South-East Trade Winds blow fairly consistently throughout the year, setting in motion the surface water to form the great North and South Equatorial Currents which flow from east to west in the Atlantic, Indian and Pacific Oceans. Across the path of these currents lie continents which deflect the water north or south.


People in every industrialized country have daily contact with pollution problems Climate gas emissions are already almost certainly the cause of most extreme weather events. Between 80 and 90 of all cases of cancer are influenced by environmental factors and the prevalence of allergies is rapidly increasing. At the same time, the rate of extinction of animal and plant species is accelerating -between 1900 and 1950 one species each year disappeared, while in 1990 alone, between one and three species disappeared every hour. Species have always died out and new ones have appeared, but the rate of extinction today is 100 to 1000 times greater than the natural rate (Lawton and May, 1995).

Ageing by numbers

There are several other more sophisticated non-evolutionary (or at least not directly evolutionary) explanations of ageing very similar to wear-and-tear, but in these cases the damage is associated with an intrinsic breakdown of the genetic machinery, rather than an accumulation of chemical or physical damage. Paralleling the decline in fission rates in single-celled organisms, it is now recognized that cells within a multicel-lular body can only go through a limited number of cell divisions before ceasing active division. In the case of human cells, for example, the maximum limit is in the order of 50-60 divisions. This restriction is known (in honour of its discoverer Leonard Hayflick) as the Hayflick limit.48,49 What causes these Hayflick limits Accumulation of deleterious mutations within cells may play some roles50 as well as changes in the quantity and distribution of chemicals ('epigenetic factors') which bind to DNA to influence gene expression, but a widely discussed...


Papillomaviruses are classified into types, subtypes, and variants based on the sequence of the L1 gene. They are also grouped based on sequence similarity, host type, and pathogenic characteristics. In this example, we consider the sequence of the L1 gene for thirty Group A papillomaviruses, 28 of which infect humans. Notable among this collection of sequences are human papillomavirus (HPV) types 16, 18, and 31, which are found to be associated with over 95 of cervical cancer cases 87 . The particular sequences studied here, as well as their genetic subtype and pathology, are listed in Table 1.3. More information on these particular sequences can be found in Ong et al. (1997), and information concerning the genetics of papillomaviruses in general can be found in Zheng and Baker (2006).


Carcinogen Any substance or agent that causes living tissues to become cancerous. Chemical carcinogens include many organic compounds and certain inorganic compounds such as asbestos. Physical agents that can cause cancer include radioactive materials and x-rays. Many carcinogens achieve their effect by causing mutations they are mutagens.

Genetic Disease

Cancer is a result of a series of mutations (see Section 6.2.3). If some of these are inherited, a person is more susceptible to cancer, since fewer mutations remain to occur. For example, a gene associated with breast cancer has been discovered on chromosome 17 that is responsible for about 10 of all cases. Women with the mutation have an 80 to 90 chance of contracting the disease.


A mutation is a change in the hereditary information contained in an organism. With most mutations, if the genotypic change is expressed phenotypically, cell death results. In a few cases survival is possible, with altered function. In rare cases, the mutation may actually aid the cell. Usually, it does not. In somatic cells, some mutations may be an initiating step in the formation of cancer. In germ (reproductive) cells, mutations may be passed on to the offspring, resulting in either teratogenesis, genetic disorders, or in some cases producing cancer that develops later in the offspring. Mutations can be caused by chemical or physical agents such as natural or industrial chemicals or radiation.

DNA Repair

Some humans have an inherited autosomal recessive condition called xeroderma pigmentosum. These persons are exceedingly sensitive to getting skin cancer from exposure to sunlight. The condition can be diagnosed in infancy, enabling people to lead fairly normal lives by protecting themselves from exposure to the sun. The condition seems to be related to a number of different mutations, including about seven that affect excision repair, and to reduced activity of the enzyme that uses blue light to repair thymidine dimers.

Genetic Engineering

Another therapy on the horizon is antisense drugs, which are synthetic nucleotide polymers that bind selectively to mRNA from a particular gene, interfering with synthesis of the corresponding protein. If the mRNA structure for a protein is known, an antisense drug can be designed to be complementary to 17 to 25 of its bases. This gives the drug high specificity, and since cells may make thousands of protein molecules from each mRNA, the antisense drugs could be effective in very low doses. Antisense drugs are being designed to block expression of cancer and virus genes, as well as normal human genes in special cases. However, delivery of these drugs to the cell interior is a problem.

PAH Toxicity

The PAHs represent a large family of compounds, ranging from the two-ringed naphthalenes to the ten-ringed derivatives of naphthalene. They can be modified by the presence of alkyl side chains or various functional groups which produce a large variety of physical-chemical properties and toxicities. While the most toxic components of oil, the MAHs, are relatively water soluble, they evaporate quickly after oil is spilled. At the other end, the nonvolatile high molecular weight PAHs cannot effectively dissolve in water. Therefore, only intermediate-sized PAHs (such as acenaphthene, phenanthrene, and fluoranthene) significantly influence the toxicity of oil to pelagic organisms in the water column. PAHs can lead to both carcinogenic and noncarcinogenic effects such as oxidative stress, suppression of the immune system, and impairment of endocrine regulation and development. They are metabolized by cytochrome P450 isozymes to reactive metabolites such as epoxides, which target...

Nervous System

The primary functional components of the nervous system are the nerve cells, or neurons. They can have many shapes Figure 9.2 shows a common type. The main parts are the cell body, or soma, the highly branched dendrites, and the axon. The soma contains the nucleus and cytoplasm, with its typical cell machinery, such as mitochondria and ribo-somes. The neuron lacks a centriole, which makes it impossible for it to divide. Thus, neurons cannot regenerate once damaged. This also means that neurons cannot become cancerous. Brain cancer in adults occurs in other nervous system cells, called glial cells. The dendrites provide most of the sites for the reception of nerve signals. The axon is a long extension of the cell that serves to transmit the nerve signal over a great distance. It may have branches, and it is often sheathed in a lipid coating called myelin that serves as an insulator for the signal transmission. Neurons transmit signals from one cell to another at a specialized point of...


Unlike the traditional dose-response in humans with definite assessed endpoint, for example, cancer resulting from exposure to environmental carcinogens, responses in ecological risk assessment vary considerably and can be a source of contention even when experimental evidence exists that links the stressor under consideration to the effects. The reason for this is not unconnected to the social and political legal dimension that often comes to bear on ecological risk analyses, not the least of which are

Synergistic response

Synergistic response describes a situation where one component is concentrated enough to cause toxic effect by itself but the presence of another causes a much greater effect than the combined effects of the individual components. Sometimes two substances may have effects which reinforce each other so much that the combined effect is more than the additive. For example, tobacco smoke in combination with asbestos dust can cause lung cancer in humans more readily than exposure to either the cigarette smoke or asbestos dust alone. In fact, it has been documented that smokers are 40 times more likely than nonsmokers to get lung cancer following exposure to asbestos dust. In this case, the response is greater than additive toxicity (2 + 2 6). Another classical example of a synergistic effect is the formation of trihalomethane known to cause cancer in humans. Trihalomethane is a compound formed from chlorine used as disinfectants for microorganisms in water when it reacts with suspended...

Cells and Tissues

Cancer is a cellular response to carcinogen exposure that is carefully studied by ecotoxicologists. Several ecological studies have demonstrated the role of environmental toxicants on cancer etiology. For example, Puget Sound English sole (Parophrys vetulus) taken from sites with elevated sediment contamination showed high prevalence of liver cancers. Another case of elevated cancer prevalence (27 of dead adults) involved beluga whales (Delpinapterus leucas) inhabiting a contaminated reach of the St. Lawrence estuary. Toxicant effect on organs and organ systems is another major theme in classical toxicology that also has a role in ecotoxicology. Organs can be targets of toxicant effects as in the case of the liver cancer mentioned above or can be routes of toxicant entry into the body as in the case of the integument, breathing organs, and digestive tract. Exposure studies at this level ofbiological organization emphasize target organs. Some organs or organ systems are more prone to...

Wildlife Studies

For many decades, there has been concern about the effects of environmental contaminants on the health and persistence of wildlife populations. Prior to work over the last 10-15 years, the vast majority of these studies examined the lethal consequences of exposure, or they focused on the induction of cancer or major birth defects. Although these endpoints are still critical in the study of toxicology, a growing collection of studies examining diverse wildlife species demonstrates that additional adverse outcomes can be produced in wildlife as a result of exposure to environmental contaminants. A number of these abnormalities have been attributed to the disruption of endocrine signaling. Below, we examine a few of the many examples of endocrine disruption in wildlife.

Theoretical Concepts

To permanently interfere with gene expression and other cellular activities, resulting in abnormalities and disease that becomes apparent in adulthood . Thus, while some functional deficits and disease states are due to inherited mutations in genetic makeup, many diseases may also be associated with alterations in gene expression. These alterations relate to differential methylation of cytosine in the 5' region of the promoter (where the presence of methyl-cytosine leads to gene silencing) as well as changes in acetylation methylation of histone proteins that determine whether genes are able to be activated by transcription factors. These chemical modifications of chromatin and DNA are referred to as 'epigenetic' changes and are now recognized as a major factor in the process of cell differentiation as well as the ontogeny of cancer, in contrast to classical mutations, which involve base deletions and substitutions. Altered gene expression and cellular signaling subsequent to...


The effect of quiescent states may be significant with respect to outcomes in specific biological systems. In fact, quiescent phases can have a quite surprising effect on the population as a whole. For example, quiescent states can induce taxis terms in movement equations. The extinction of populations (through washout) in river ecosystems can be prevented when there is a stationary phase weakly coupled to the mobile state. Cancer tumors can resist radiation treatment when cells have refuge in a quiescent state, which needs to be accounted for in radiation treatment planning. A similar effect is known for antibiotic resistance in bacteria. Balaban et al. (2004) have used a model involving a quiescent state (they called it persisters) to fit survival data of E. coli bacteria which were exposed to the antibiotic ampicillin. They show that the existence of a persisting compartment can explain population survival and re-growth after treatment.


A continuum of larval migration by crab species results in horizontal zonation of species in the plankton between the upper estuary and the edge of the continental shelf Rhithropanopeus harrisii larvae occur in the upper estuary, Dyspanopeus sayi larvae occur in the mid to lower estuary, Libinia spp. larvae occur in the lower estuary to the plume front, Ovalipes ocellatus and Uca spp. larvae occur from the upper, mid, or lower estuary (depending on the species) to the inner shelf, Callinectes sapidus larvae occur from the lower estuary to the outer shelf, and Cancer spp. larvae occur on the shelf. Larval migration by fishes also results in a predictable spatial gradient with larvae either largely remaining in the estuary, remaining on the shelf, or migrating from the shelf to the estuary Anchoa mitchelli and Gobiosoma bosc larvae primarily occur in the estuary, Pomato-mus saltatrix larvae occur on the shelf and enter the estuary as postlarvae, and nonestuarine-dependent...

Other Agents

Fungi Several types of fungi can cause food poisoning. Some wild mushrooms are themselves highly poisonous, but may be mistaken for edible varieties by inexperienced pickers. On the other hand, growth of fungi within a food material can produce toxins. Ergotism, as described in Section 10.7.4, for example, is caused by the neurotoxins produced by the ascomycete Claviceps purpurea in infected cereal grains (especially, rye). Similarly, the aflatoxins produced by some strains of Aspergillus, particularly during growth on stored grains and peanuts, are potential carcinogens (cancer-causing agents). However, infection by ingested fungi is rare.

Hepatitis B

Hepatitis B, or serum hepatitis, is spread mainly through contaminated blood, often from unsterilized needles shared by drug users or used for tattoos or ear or body piercing. The virus can also be transmitted sexually. Over 100,000 people are infected yearly in the United States, but this number is decreasing due to the recent introduction of a vaccine. In addition to the initial disease, which is more severe than hepatitis A (more liver damage and fatality rate of 10 ), those infected are at higher risk of liver cancer.


UV Radiation Overexposure to the Sun's radiation can cause health problems such as cataracts, which cloud the lens of the eye, and skin cancer. In your Science Journal, describe ways to limit your exposure to the Sun's damaging radiation. Ozone Depletion The atmosphere includes the ozone layer ozone gas that is about 15 km to 30 km above Earth's surface. It protects life on Earth by preventing damaging amounts of the Sun's ultraviolet (UV) radiation from reaching Earth's surface. Scientists have discovered that the ozone layer is gradually becoming thinner. The thinning of the ozone layer is called ozone depletion. This depletion allows increased amounts of UV radiation that can harm living organisms to reach Earth's surface. For humans, it could mean more cases of skin cancer. Ozone depletion occurs over much of Earth. Data collected in the late 1990s indicate that ozone levels over the United States, for example, had decreased by five to ten percent since the 1970s.

Wetlands Animals

The simpler animals are osmoconformers they adjust their cell osmolarity in response to the external salinity. More complex animals are osmoregulators, which maintain their internal environment in the face of external changes. The difference depends on the ability of the organism to excrete salt. In crabs it also depends on the permeability of the shell to salt. Crabs such as Cancer are always submerged they have a more permeable shell and are an osmoconformer. Crabs that spend part of their time out of the water, such as Uca spp., are excellent osmoregulators. Their shells are relatively impermeable to salt. Other species fall in between.

Coral reefs

Coral reefs are found in tropical and sub-tropical areas where the average minimum temperature is not less than 20oC and so are found mainly between the Tropics of Cancer and Capricorn where water temperatures remain steady all year round. They are not able to withstand any great fluctuations in temperature and recent episodes of coral bleaching have been associated with rises in water temperature (see Section 10.2.3). The approximate worldwide distribution of coral reefs is shown in Figure 8.18, from which it can be seen that no reefs are found up the west coast of Africa, although this coast lies within the tropics. The reason for this is the occurrence of the Benguela current (see Figure 1.6) which carries cold water northwards from Antarctic waters. Wherever cold currents intrude into the tropics, corals will not thrive. Likewise, where significant amounts of fresh water flow into the sea from major rivers such as the Amazon, growth of coral reefs is also severely limited. Reefs...

The system

Studies in chemistry, or any realm of science, commonly consist of a series of directed examinations of parts of nature's realm called systems. A system is an identifiable fragment of the world that is recognizable and that has attributes that one can identify in terms of form and or function. We can give examples at any level of size and complexity, and in essentially any context. Indeed, a dog is a system at a pet show whereas the human heart is a system to the cardiologist a tumor cell is a system to the cancer specialist a star or planet or galaxy is a system to an astronomer a molecule, or a collection of molecules, is a system to a chemist and a macromolecule in a cell is a system to a molecular biologist. A system is, then, whatever we choose to focus our attention upon for study and examination.

Dungeness Crab

Cancer magister Present for more than 450 million years, coral reefs sit beneath shallow, warm ocean waters between the Tropics of Cancer and Capricorn. Coral reefs are veritable rainforests of the sea their biodiversity encompasses almost one-third of all ocean species. The reefs are solid structures composed primarily of coral rock formed from the calcium carbonate secreted by coral polyps. Many organisms contain very potent biochemical substances.

The Role of Ozone

Ozone in the stratosphere is often called 'good' ozone because it protects life on Earth from harmful levels of UV radiation from the Sun. Therefore, a decrease in the amount of ozone would allow an increase in the amount of the UV radiation from the Sun to reach the Earth's surface. Corresponding to an increase in UV are projected significant impacts on ecosystems and human health, including increases in incidences of skin cancer, eye cataracts, damage to genetic DNA, and suppression of the efficiency of the immune system. It is the concerns about increased biologically harmful levels of UV from the decreasing levels of ozone that has largely been the driver for policy actions to protect the ozone layer.

Organismal Responses

Figure 5 Comparison of intensity of incident UV wavelengths (solid red line) and generalized biological inactivation curve (blue line, data from Tyrrell RM and Pidoux M (1987) Action spectra for human skin cells Estimates of the relative cytotoxicity of the middle ultraviolet, near ultraviolet, and violet regions of sunlight on epidermal keratinocytes. Cancer Research 47 1825-1829). The estimated shift in UVB wavelength and intensity with 50 ozone depletion is represented by the interrupted red line. The electromagnetic spectrum shows the full scale of solar radiation at the top of the atmosphere. Incident radiation falls within the wavelengths bracketed by the yellow bar. Figure 5 Comparison of intensity of incident UV wavelengths (solid red line) and generalized biological inactivation curve (blue line, data from Tyrrell RM and Pidoux M (1987) Action spectra for human skin cells Estimates of the relative cytotoxicity of the middle ultraviolet, near ultraviolet, and violet regions of...


Given the biological activities of terpenes, it is not surprising that many have significant practical applications. The diterpene Taxoltm is now considered one of the most efficacious agents for a range of cancer types,10 and artemisinin, a sesquiterpene, is a promising lead agent for the treatment of malaria.11 Agricultural uses for terpenes include insect and microbe control agents12 and additives for many food applications.13 Terpenes are also used in industrial lubricants and as paint additives.1415


Mutations were described in Section 6.2.3. Agents that can cause mutations are called mutagens. Mutations can result in hereditable diseases, birth defects, or cancer. According to one study, 90 of carcinogens show mutagenic activity in a microbial assay (the Ames test, Section 20.1.12). The same study found that few noncarcinogens are muta-genic. The correlation between mutagenicity in laboratory tests and that in humans is highly uncertain. Nevertheless, prudence dictates that substances known to be mutagenic in appropriate laboratory models should be presumed to present a high risk to humans as well.