Metabolism of benzo(a)pyrene (BaP) in vivo and in vitro was studied using two benthic fish species, English sole (Parophrys vetulus) and starry flounder (Platichthys stellatus), and Sprague-Dawley rats. At 24 h after administration of BaP (7.9 µmol/kg of body weight) to fish either p.o. (Experiment 1) or i.p. (Experiment 2), the specific activity of binding of BaP metabolites to hepatic DNA (pmol of BaP equivalent per mg of DNA) was higher in sole [2.1 in Experiment 1; 28 ± 5 (SE) in Experiment 2] than in flounder (0.5 in Experiment 1; 14 ± 4 in Experiment 2). Treatment of bile with β-glucuronidase and arylsulfatase released a significantly higher proportion of 7,8-dihydroxy-7,8-dihydro-BaP (BaP 7,8-diol) from sole bile than from flounder bile in both experiments. However, the rate of BaP metabolism and rate of formation of BaP 7,8-diol by hepatic microsomes were comparable for both fish species. Thus, the differences in both the level of DNA binding and the concentration of BaP 7,8-diol in bile of BaP-exposed sole and flounder were apparently due to differences in detoxication, rather than formation, of BaP 7,8-oxide and BaP 7,8-diol-9,10-epoxide.

The rate of formation of BaP 7,8-diol by rat liver microsomes (28 ± 1 pmol of BaP 7,8-diol formed per min per mg of protein) was comparable to that by hepatic microsomes from both fish species (50 ± 10 for sole and 33 ± 6 for flounder), although the rate of BaP metabolism (600 ± 200) was approximately 3 times greater than that by the fish species (190 ± 60 for sole and 180 ± 40 for flounder). Thus, greater proportion of BaP was converted to BaP 7,8-diol by liver microsomes of fish species than rat. These differences in BaP metabolism in vitro help explain, in part, the substantially lower binding (0.3 ± 0.1; Experiment 2) for hepatic DNA in BaP-exposed rat than that in either sole or flounder.


This project has been funded at least in part with Federal funds from the Department of Health and Human Services under Interagency Agreement Y01-CP-40507. This work was presented, in part, at the 76th Annual Meeting of the American Association for Cancer Research, Houston, TX, 1985 (43).

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