MOLECULAR EPIZOOTIOLOGY OF GENOTOXIC EVENTS IN MARINE FISH - LINKING CONTAMINANT EXPOSURE, DNA-DAMAGE, AND TISSUE-LEVEL ALTERATIONS

Molecular epizootiological studies are increasingly being used to inve stigate environmental effects of genotoxic contaminants. The assessmen t of damage to DNA and linking the damage to subsequent molecular, cel lular, or tissue-level alterations is a central component of such stud ies. Our research has focused on the refinement of the P-32-postlabeli ng assay for measuring covalent DNA-xenobiotic adducts arising from ex posure to polycyclic aromatic compounds, using DNA adducts as molecula r dosimeters of genotoxic contaminant exposure in biomonitoring studie s, and investigating the relationship of DNA adduct formation to toxic opathic liver disease, including neoplastic lesions. A combination of field and laboratory studies using the P-32-postlabeling assay has sho wn that DNA adducts in marine fish are effective molecular dosimeters of genotoxic contaminant exposure. Investigations of the relationship of DNA adduct formation to neoplastic liver disease have shown that el evated levels of DNA adducts in certain fish species from contaminated coastal sites are associated with increased prevalences of toxicopath ic hepatic lesions, including neoplasms, and that the ability to asses s DNA damage has helped to explain, in part, species differences in le sion prevalence. Moreover, in a study of a site in Puget Sound contami nated with polycyclic aromatic compounds, we have shown, for the first time, that elevated levels of hepatic DNA adducts are a significant r isk factor for certain degenerative and preneoplastic lesions occurrin g early in the histogenesis of hepatic neoplasms in feral English sole (Pleuronectes vetulus). These latter findings coupled with our curren t studies of mutational events in the K-ras proto-oncogene should prov ide further mechanistic substantiation that mutagenic events resulting from exposure to complex mixtures of genotoxic polycyclic aromatic co mpounds are involved in the etiology of hepatic neoplasia in English s ole. (C) 1998 Elsevier Science B.V. All rights reserved.