Use of biomarkers to determine the etiology of cancer in tomcod

Biomarkers provide an indirect approach to address the etiology of perturbations in natural populations. Biomarkers are quantitative endpoints, usually measured in sentinel species, of exposure to and biological effects of stressors. If significantly induced biomarker responses occur at mechanistically linked hierarchical steps of biological organization, a weight of evidence approach may be used to infer cause of perturbations at the organ-ismic, population, or community levels. Thus, the objective of biomarker studies is to demonstrate significant responses in ecosystems at endpoints from the molecular through the population/ community levels. Molecular biomarkers can provide a direct link between exposure and effects but may be of low ecological relevance, whereas it is more difficult to establish cause and effect relationships between exposure andresponses at thepopu-lation/community levels but alterations are of high ecological importance. A biomarker approach was used to explain the high prevalence of tumors in tomcod from the HR.

Tomcod from the HR are exposed to much higher levels of classes of xenobiotics that initiate and promote chemically-induced neoplasia than tomcod from elsewhere. Metabolites of PAHs "initiate" chemical carcinogenesis by inducing DNA lesions and signature mutations at sensitive oncogenes and tumor suppressor genes. It is difficult to directly measure PAH levels in fish tissues because of their rapid metabolism. However, a quantitative, indirect measure of exposure to high molecular weight PAHs, fluorescent aromatic compounds (metabolites of PAHs) (FACs) in bile, was developed. Adult and juvenile tomcod from the HR exhibited six to eight-fold higher levels of FACs than tomcod from four cleaner estuaries confirming the bioavailability of PAHs to the HR population and their metabolism (Wirgin et al., 1994).

PCBs and PCDD/Fs "promote" chemical carcinogenesis by enhancing the growth of cells with damaged DNA at the expense of nearby normal cells that are more sensitive to the toxicity of these compounds. Unfertilized eggs (Roy et al., 2001) and livers of juvenile (Yuan et al., 2001) and adult (Courtenay et al., 1999) tomcod from the HR estuary exhibit much higher levels of these contaminants than tomcod from elsewhere, sometimes at world-record levels. For example, hepatic burdens of the most toxic dioxin congener, TCDD, in six-month old tomcod from the Newark Bay complex ranged between 897 and 655 ng/kg body wt (Yuan et al., 2001) indicating that the population is exposed at early, presumably sensitive life stages. These levels of TCDD were 10 to 500-fold higher than in matched tomcod from the cleanest river tested, the Margaree River in Nova Scotia. Similarly, wet weight levels of toxic coplanar PCBs were 40 to 100-fold higher in tomcod from the

HR, compared to those from two cleaner rivers in Canada (Courtenayetal., 1999).

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