Overview of studies on liver carcinogenesis in English sole from Puget Sound; evidence for a xenobiotic chemical etiology. II: Biochemical studies

Abstract

The levels of aromatic hydrocarbons in sediments of Puget Sound, Washington, are positively correlated with the prevalence of hepatic neoplasms and related lesions in English sole (Parophrys vetulus). To investigate the biochemical processes involved in chemical carcinogenesis in fish from Puget Sound, we have studied the uptake, activation, and detoxication of polycyclic aromatic hydrocarbons (PAHs) in English sole, and have compared these data to PAH metabolism in a related species, starry flounder (Platichthys stellatus), which shows a lower prevalence of hepatic neoplasms than sole. The results of both laboratory and field studies show that sediment-associated PAHs are biologically available to both flatfish species, and that both species accumulate similar levels of PAHs. Analyses of hepatic DNA from sole using the 32P-postlabeling technique indicate that xenobiotic chemicals were adducted to hepatic DNA of fish from the contaminated sites but not to the DNA of fish from reference sites. Studies of the ability of English sole and starry flounder to metabolize benzo(a)pyrene (BaP) and bind reactive BaP intermediates to hepatic DNA indicate that biochemical differences in the metabolism of carcinogenic PAHs may explain, at least in part, the apparent lower susceptibility of starry flounder than English sole to chemically induced hepatocarcinogenesis.