Dibenz [a,j]acridine: distributions of metabolites formed by liver and lung microsomes from control and pretreated rats.
The structures of many dibenz[a,j]acridine (DBAJAC) metabolites formed in vitro in incubations with liver microsomes prepared from 3-methylcholanthrene-pretreated male Wistar rats have previously been determined; they were trans-DBAJAC-3,4-dihydrodiol, trans-DBAJAC-5,6-dihydrodiol, DBAJAC-5,6-oxide, 3-hydroxy-DBAJAC, 4-hydroxy-DBAJAC and several multiply oxidized secondary metabolites. Herein are reported [14-3H]DBAJAC metabolite distributions obtained by h.p.l.c. separation of products produced in incubations with liver and lung microsomes prepared from untreated, phenobarbital-pretreated and 3-methylcholanthrene-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 carcinogen 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 incubations conducted in the presence of 3,3,3-trichloropropene-1,2-oxide (1.5 mM) formation of dihydrodiol was inhibited by about 85%. DBAJAC-N-oxide was also identified as a minor metabolite (approximately 1%) formed in incubations with phenobarbital-induced and control liver microsomes.
D000166:Acridines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013267:Stilbenes / Q000494:pharmacology*
D000166:Acridines; D013267:Stilbenes; C022289:dibenzacridine; D008748:Methylcholanthrene; C025906:stilbene oxide; D010634:Phenobarbital