Because most environmentally induced mutations originate as DNA damage, any discussion on mutagenesis must begin with a discourse on this subject. For the sake of clarity, the structure of DNA bases is given in Figure 1.
Table 1 Examples of common mutagenic and genotoxic chemicals, their sources in the environment, and the mechanism of formation of DNA damage
Polycyclic aromatic hydrocarbons
Alkylating agents, nitrosamines
Halogenated organics (PCBs, dioxins, chlorinated solvents, perfluorocarbons, brominated aromatic hydrocarbons)
Transition metals, heavy metals, and arsenic
Combustion of organic matter and fossil fuels, crude oil and coal spills and leaching, copier toner cartridges, coal coking, creosote, used oil and lubricants, asphalt
Rubber industry, dyes
Industrial manufacturing, paper processing, electrical insulators, cleaning and degreasing agents, solvents, chemical industry, combustion and manufacture of plastics, flame retardants, stain repellents
Agricultural, commercial, and residential applications
Industrial manufacturing, agricultural chemicals, ore mining and smelting, steel manufacture, building materials and paints, gasoline additives, fossil fuel extraction, combustion of coal, battery manufacture and disposal, metal plating, photographic emulsions, paper manufacture
Uranium ore mining and fuel processing, nuclear energy, nuclear weapons, combustion of coal
Methylated or ethylated bases
Oxidative damagea,b Adducts
Methylated or ethylated bases (some)
Oxidative damage,a,b base loss and fragmentation, DNA-DNA cross-links
Pyrimidine dimers, 6-4 photoproducts
Metabolic activation Induction of cytochrome P450 Formation and redox cycling of quinones
Induction of cytochrome P450 Interference with mitochondrial function Modification of peroxisome function
Induction of cytochrome P450 Redox cycling (diquat) Interference with mitochondrial function Modification of peroxisome function Metabolic activation
Reduction of O2 to form superoxided Reduction of hydrogen peroxided Catalysis of quinone redox cyclingd Interference with mitochondrial metabolism Inhibition of DNA repair Inhibition of antioxidant enzymes Glutathione depletion
Direct DNA binding
Formation of oxyradicals from water and oxygen
Excitation of oxygen to singlet oxygen Direct interaction of radioactive particle with DNA sugars and bases
Excitation of oxygen to singlet oxygen Interaction of UV light with bases aAdducts and oxidized bases may lead to production of abasic sites via destabilization of the glycoside (sugar base) linkage.
^Oxidative damage includes oxidized bases, change in chemical structure of bases (e.g., open rings), strand breaks, base loss, DNA-protein adducts, and lipid aldehyde adducts.
cIncludes insecticides (organochlorines, organophosphates, carbamates, pyrethroids), herbicides, and fungicides. ^Transition metals only.
Many classes of DNA damage can lead to mutations, as illustrated in Figure 2. Such DNA lesions include damage to DNA bases or to the deoxyribose sugar, base loss, strand breakage, and DNA cross-links (Figure 2).
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