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National Institute of Environmental Health Sciences

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Publication Detail

Title: Pyrrolizidine alkaloid-induced alterations in benzo[alpha]pyrene metabolism and binding of benzo[alpha]pyrene metabolites to deoxyribonucleic acid.

Authors: Williams, D E; Miranda, C L; Buhler, D R

Published In Biochem Pharmacol, (1983 Aug 15)

Abstract: Pretreatment of rats by oral administration of jacobine, a pyrrolizidine alkaloid and inducer of epoxide hydrolase, produced a marked shift in hepatic microsomal metabolism in vitro of benzo[alpha]pyrene. The formation of 9-hydroxybenzo[alpha]pyrene and 7,8-dihydroxy-7,8-dihydrobenzo[alpha]pyrene was decreased whereas the formation of 4,5-dihydroxy-4,5-dihydrobenzo[alpha]pyrene was increased following jacobine treatment. This shift in the ratio of benzo[alpha]pyrene metabolites was accompanied by a significant reduction in DNA binding. Addition of purified epoxide hydrolase to control or jacobine microsomes produced a similar decrease in total DNA binding. Chromatography of benzo[alpha]pyrene metabolite-DNA nucleoside adducts showed a marked reduction in four peaks and the elimination of one peak with microsomes from jacobine-treated rats.

PubMed ID: 6311218 Exiting the NIEHS site

MeSH Terms: Animals; Benzo(a)pyrene; Benzopyrenes/metabolism*; DNA/metabolism*; In Vitro Techniques; Male; Microsomes, Liver/metabolism; Pyrrolizidine Alkaloids/pharmacology*; Rats; Rats, Inbred Strains

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