Comparative metabolism of benzo(a)pyrene and covalent binding to hepatic DNA in English sole, starry flounder, and rat

• Published in: Cancer research (Chicago, Ill.) Vol. 46; no. 8; pp. 3817 - 3824
• Main Authors: VARANASI, U, NISHIMOTO, M, REICHERT, W. L, LE EBERHART, B.-T
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.1986
• Subjects: Animals; Benzo(a)pyrene - metabolism; Benzopyrenes - metabolism; Bile - metabolism; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Chromatography, High Pressure Liquid; Dihydroxydihydrobenzopyrenes; DNA - metabolism; Fishes - metabolism; Glutathione - metabolism; Glutathione Transferase - analysis; Liver - metabolism; Liver Neoplasms, Experimental - chemically induced; Medical sciences; Rats; Rats, Inbred Strains; Species Specificity; Tumors; Intraperitoneal administration; Rat; Liver; Rodentia; Oral administration; Molecular interaction; Polycyclic aromatic compound; Metabolism; Carcinogen; Vertebrata; Mammalia; Animal; DNA; Pisces; Covalent bond; Mechanism of action
• ISSN: 0008-5472; 1538-7445

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 mumol/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 beta-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.