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© 1987 Oxford University Press

research-article

Dibenz[a,j]acridine: distributions of metabolites formed by liver and lung microsomes from control and pretreated rats

Jennifer H. Gill, Colin C. Duke, Adrian J. Ryan and Gerald M. Holder 1

Department of Pharmacy, The University of Sydney NSW 2006, Australia

1To whom reprint requests should be sent

The structures of many dibenz[a,j]acridine (DBAJAC) metabolites formed in vitro in incubations with liver microsomes prepared from 3-methyicholanthrene-pretreated male Wistar rats have previously been determined; they were trans-DBAJAC-3,4-dihydrodiol, trans-DBAJAC-5,6-dihydro-diol, DBAJAC-5,6-oxide, 3-hydroxy-DBAJAC, 4-hydroxy-DRAJAC and several multiply oxidized secondary metab olites. Herein are reported [143]DBAJAC metabolite distributions obtained by h.p.l.c. separation of products pro duced in incubations with liver and lung microsomes prepared from untreated, phenobarbital-pretreated and 3-methyl-cholanthrene-pretreated male Wistar rats. Liver microsomal metabolites were also quantitated in preparations from trans stilbene oxide-pretreated rats. For all preparations trans DBAJAC-3,4-dihydrodiol, the candidate proximate car cinogen according to the bay-region theory of carcinogenesis, was the major metabolite (30–40%) while DBAJAC-5,6-oxide and phenols were also quantitatively important. In incuba tions conducted in the presence of 3,3,3-trichloropropene- 1,2-oxide (1.5 mM) formation of dihydrodiol was inthibited by about 85%. DBAJAC-N-oxide was also identified as a minor metabolite (~1%) formed in incubations with pheno barbital-induced and control liver microsomes.


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