Relationships between hepatic neoplasms and related lesions and exposure to toxic chemicals in marine fish from the U.S. 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 in 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Consistent associations between hepatic lesions in English sole (Parophrys vetulus) and polycyclic aromatic hydrocarbons in bottom sediment.

A consistent and statistically significant association between prevalence of hepatic neoplasms in free-living sole (Parophrys vetulus) and levels of anthropogenic polycyclic aromatic hydrocarbons in bottom sediment from sites of fish capture was documented in a series of studies conducted over a period of 7 years in Puget Sound, Washington. This result strengthens the evidence supporting a causal relationship between exposure to sediment-associated hydrocarbons and development of hepatic neoplasms in this bottom-dwelling marine fish species. Prevalences of two other distinct categories of idiopathic hepatic lesions-megalocytic hepatosis and steatosis/hemosiderosis-also showed consistent, statistically significant associations with polycylic aromatic hydrocarbon concentrations in bottom sediment, and association with prevalence of a third category (putatively preneoplastic foci of cellular alteration) approached statistical significance. On the basis of other studies, megalocytic hepatosis and foci of cellular alteration are both considered to be important precursor lesions in the stepwise histogenesis of hepatic neoplasms.

Overview of studies on liver carcinogenesis in English sole from Puget Sound; evidence for a xenobiotic chemical etiology. I: Pathology and epizootiology.

Livers of wild English sole (Parophrys vetulus) from polluted waterways and embayments of Puget Sound, Washington, are affected by a spectrum of multiple, co-occurring idiopathic hepatic lesions, including neoplasms, putative preneoplastic foci of cellular alteration, and unique degeneration conditions. Results from a statistical analysis of the patterns of co-occurrence of these lesions in wild English sole indicate that these lesions represent morphologically identifiable steps leading to the development of hepatic neoplasms. This sequence parallels the lesion progression in experimental models of chemically induced liver carcinogenesis in rodents. The hypothesis that these lesions in wild English sole can be caused by exposure to certain xenobiotic hepatotoxic and hepatocarcinogenic compounds in Puget Sound is based on: a) statistical associations between levels of aromatic hydrocarbons (sigma AHs) in sediment and prevalences of these idiopathic liver lesions, b) the contribution of sigma AHs in accounting for the variability in hepatic neoplasm prevalence in a logistic regression model, c) elevated odds ratios for several idiopathic hepatic lesion types in sole from polluted sites in Puget Sound, d) significant correlations between prevalences of idiopathic hepatic lesions and levels of fluorescent metabolites of aromatic compounds (FACs) in bile of English sole, and e) experimental induction of putatively preneoplastic focal lesions in English sole injected with a PAH-enriched fraction of an extract from a contaminated urban sediment from Puget Sound, that were morphologically identical to lesions found in wild English sole from the same site.

Field and laboratory studies of the etiology of liver neoplasms in marine fish from Puget Sound.

A series of field studies was conducted between 1979 and 1985 in Puget Sound, Washington State, to investigate etiological relationships between prevalences of hepatic neoplasms in bottom-dwelling marine fish species, with emphasis on English sole (Parophrys vetulus), and concentrations of toxic chemicals in sediments and affected fish. Statistically significant (p less than or equal to 0.05) correlations have been found between the prevalences of hepatic neoplasms in English sole and the following parameters: sediment concentrations of aromatic hydrocarbons, and concentrations of the metabolites of aromatic compounds in the bile of affected sole. A significant difference (p less than 0.001) was also found between the relative concentrations of aromatic free radicals in the liver microsomes of English sole with liver lesions compared to sole without liver lesions. Laboratory studies designed to evaluate the etiology of the liver neoplasms in English sole have also yielded evidence that is consistent with the view that high molecular weight aromatic hydrocarbons, e.g., benzo[a]pyrene (BaP), are hepatocarcinogens in English sole. The current status of a series of long-term (up to 18 months) exposures of English sole and rainbow trout (Salmo gairdneri) to selected fractions of Puget Sound sediment extracts, enriched with aromatic hydrocarbons and nitrogen-containing aromatic compounds, and to individual carcinogens (e.g., BaP) is discussed.