ALTERED GENE-EXPRESSION AND GENETIC-DAMAGE IN NORTH-AMERICAN FISH POPULATIONS

Populations of marine, estuarine, and freshwater fish from highly urba n and industrialized sites in North America often exhibit elevated pre valences of neoplastic, preneoplastic, and nonneoplastic hepatic lesio ns, and sometimes epidermal neoplasms compared to conspecifics from mo re pristine reference locales. Positive statistical associations with environmental concentrations of PAHs and other xenobiotics and experim ental laboratory studies suggest a chemical etiology to these epizooti cs. Studies have investigated the expression of carcinogenically relev ant genes, the extent of overall DNA damage, somatic cell mutations, g erm line polymorphisms, and overall levels of genetic diversity in fis h from these populations and other polluted sites. In general, elevate d levels of cytochrome P4501A expression have been found in fish from contaminated locales; however, inhibition of gene induction has been s een in hepatic lesions and in normal tissue in fish from the most cont aminated sites, perhaps due to genetic adaptation or physiological acc limation. Levels of bulky hepatic DNA adducts, as detected by P-32-pos tlabeling, are almost always elevated in fish from populations that an exposed to highly contaminated environments. However, levels of DNA a dducts were not always predictive of the vulnerability to neoplasia of populations and species from polluted sites. Elevated levels of oxyge n radical-induced DNA Carnage have been observed in hepatic tumors, pr eneoplastic lesions, and normal livers in a single species of flatfish from contaminated sites; however, the prevalences of these alteration s in other species and at other polluted sites has yet to be evaluated . Frequent alterations in the K-ras oncogene have been reported in hep atic neoplasms in several species fi-om highly contaminated sites and also in embryos that were experimentally exposed to oil-con:aminated s ediments. Studies also suggest that heritable germ line polymorphisms, altered allelic frequencies, and reductions in overall genetic divers ity may have occurred in some highly impacted populations; however, th e origin and functional significance of altered allelic frequencies ha ve largely yet to be evaluated. In summary, feral fish appear particul arly sensitive to DNA alterations from xenobiotics, perhaps due to the ir unusually high levels of exposure, relatively inefficient DNA repai r, and the high frequency of polyploidy in some taxa and provide excel lent models to explore the relationships between xenobiotic exposure a nd altered gene structure and expression. (C) 1998 Elsevier Science B. V. All rights reserved.