INTERACTION OF CADMIUM AND BENZO[A]PYRENE IN MUMMICHOG (FUNDULUS-HETEROCLITUS) - BIOTRANSFORMATION IN ISOLATED HEPATOCYTES

Exposure of mummichog (Fundulus heteroclitus), a common estuarine fish species, to simultaneous doses of cadmium (Cd) and benzo[a]pyrene (BP ) has been shown to alter the acute toxicity of BP. In this study the effects of in vivo exposure to Cd and BP on the biotransformation of B P by isolated hepatocytes were investigated. Fish were injected intrap eritoneally with sublethal closes of BP and Cd, and hepatocytes from t hese fish were isolated on days 3, 7 and 14, Hepatocytes were then co- incubated with radiolabeled BP. BP breakdown, and the formation of aqu eous and organic solvent-extractable metabolites were quantified using HPLC. After three days there was a significant increase in metabolism in the BP exposed fish. The same increase was still noticeable oil da l 7, but started to return to baseline values on day. In the combined BP/Cd treated fish, BP metabolism was not significantly induced on day 3, but full indiction was reached on day 7, and was still at this lev el on day 14. Analysis of the nonconjugated metabolites showed that he patocytes produced predominantly BP-9,10-diol, BP-7,8-diol, BP-4,5-dio l, and 9-hydroxy-BP. The results of this study suggest that Cd does no t influence the profile of generated BP metabolites. However, the init ial rate of BP breakdown is significantly decreased by preexposure to cadmium. (C) 1998 Elsevier Science Ltd. All rights reserved.