RELATIONSHIPS BETWEEN HEPATIC NEOPLASMS AND RELATED LESIONS AND EXPOSURE TO TOXIC-CHEMICALS IN MARINE FISH FROM THE UNITED-STATES WEST-COAST

English sole (Parophrys vetulus) inhabiting polluted waterways and embayments of Puget Sound, Washington, are affected with a variety of multiple, co-occurring idiopathic hepatic lesions, including unique degenerative conditions, putatively preneoplastic foci of cellular alteration, and neoplasms. Results of a statistical analysis of the patterns of co-occurrence of these lesions on wild English sole are consistent with the concept that these lesions represent morphologically identifiable steps forming a sequence of progression ultimately leading to the development of hepatic neoplasms. This progressive sequence parallels the pattern identified in experimental models of chemically induced hepatocarcinogenesis in rodents. The rationale for the hypothesis that these lesions in wild English sole can be caused by exposure to certain hepatoxic and hepatocarcinogenic xenobiotic compounds in the marine environment is based on the demonstration of significant and consistent statistical associations between levels of aromatic hydrocarbons (AHs) in sediment and prevalences of these idiopathic liver lesions; a significant contribution by sediment AHs to the variability in hepatic neoplasm prevalence in a logistic regression model; significantly increased probabilities for several idiopathic lesions in sole from chemically contaminated sites in Puget Sound; significant correlations between uptake of polycyclic aromatic hydrocarbons, as measured by levels of fluorescent metabolites of aromatic compounds in bile of sole, and prevalences of several hepatic lesion types; and experimental induction of unique degenerative, proliferative, and putatively preneoplastic focal lesions in English sole injected with either benzo(a)pyrene or a polycyclic aromatic hydrocarbons (PAH) enriched fraction of an extract from a contaminated urban sediment from Puget Sound. Similar types of idiopathic hepatic lesions have been detected in white croaker (Genyonemus lineatus) captured from contaminated marine sites in the vicinity of Los Angeles, California. Although the evidence also suggests involvement of xenobiotic contaminants in the etiology of hepatic lesions in this species, no strong statistical association between lesion prevalence and contaminant exposure have been established, primarily due to the low prevalences of these lesions detected in white croaker. Data are not sufficient to conclusively establish the existence of a human health risk due to consumption of contaminant-exposed English sole and other fish species affected by hepatic neoplasms or related lesions. Because PAHs are extensively metabolized in the liver of fish, sensitive and reliable methods for detection of PAH metabolites in fish tissues need to be developed before credible assessments of human health risk due to consumption of PAH-contaminated fish muscle can be conducted.