The influence of cytochrome P-450 induction on the disposition of carcinogenic benzo[a]pyrene 7, 8-dihydrodiol 9, 10-epoxide in isolated cells |
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Authors: | Dock Lennart; Martinez Margareta; Jernstrom Bengt |
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Affiliation: | 1Department of Toxicology, Karolinska Institutet Box 60 400, S-104 01 Stockholm, Sweden
Institute of Environmental Medicine, Karolinska Institutet Box 60 208, S-104 01 Stockholm, Sweden |
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Abstract: | The disposition of the carcinogenic (+)-7ß, 8 -dihydroxy-9 ,10 -epoxy-7, 8, 9, 10-tetrahydrobenzoa]pyrene (+)-anti-BPDE]has been studied in isolated hepatocytes obtained from 3-methylcholanthrene-pretreatedrats. In these cells different routes are acting in concertand contribute to diol-epoxide elimination. Conjugation of (+)-anti-BPDEwith glutathione (GSH) and cytochrome P-450c-mediated metabolismof the diol-epoxide to 1- and 3-hydroxy-anti-BPDE (triol-epoxides)appears to be equally important. The reactive triol-epoxidesundergo a number of secondary reactions, including covalentbinding to cellular constituents, e.g. protein and GSH, andhydrolysis to pentahydroxyderivatives. The effective intracellularlifetime of (+)-anti-BPDE is 1 min and comparable to that previouslyobserved in hepatocytes obtained from uninduced animals. |
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