ACCUMULATION AND DOSE-RESPONSE OF HEPATIC DNA-ADDUCTS IN ENGLISH SOLE(PLEURONECTES VETULUS) EXPOSED TO A GRADIENT OF CONTAMINATED SEDIMENTS

Levels of hepatic DNA adducts and concentrations of fluorescent aromat ic compounds (FACs) in bile were measured in English sole (Pleuronecte s vetulus) exposed for up to 5 weeks to a reference sediment amended w ith a sediment containing high concentrations of polycyclic aromatic c ompounds (PACs) from Eagle Harbor, Puget Sound, WA. Levels of hepatic DNA adducts increased linearly with both concentration of sediment pol ycyclic aromatic hydrocarbons (PAHs) and length of exposure, whereas c oncentrations of biliary FACs were dose-responsive to levels of sedime nt PAHs but attained steady-state concentrations after 2 weeks of expo sure. The levels of DNA adducts and concentrations of biliary FACs in fish exposed to the reference sediment remained at baseline levels thr oughout the exposure. Formation of PAC-DNA adducts was observed in liv er of English sole injected with an extract of Eagle Harbor sediment ( EHSE) and in English sole hepatocytes incubated with EHSE or the neutr al fraction of EHSE containing predominantly PACs. In addition, DNA ad duct and biliary FAC levels measured in feral English sole captured fr om Eagle Harbor, when compared with levels measured in fish from the l aboratory sediment exposure study, also suggested accumulation of DNA adducts in the fish captured from Eagle Harbor. These findings, in con junction with previous studies showing PAC-DNA adducts are persistent in fish, suggest that a substantial proportion of PAC-induced DNA dama ge was not readily repaired in English sole, and thus, measurement of hepatic DNA adducts can be used as an indicator of cumulative exposure to genotoxic PACs.