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2126011 
Journal Article 
ROLE OF SPECIFIC CYTOCHROME-P-450 ISOENZYMES IN THE REGIO-SELECTIVE METABOLISM OF 7,12-DIMETHYLBENZ[A]ANTHRACENE IN MICROSOMES FROM RATS TREATED WITH PHENOBARBITAL OR SUDAN-III 
Mccord, A; Burnett, AK; Wolf, CR; Morrison, V; Craft, JA 
1988 
Yes 
Carcinogenesis
ISSN: 0143-3334
EISSN: 1460-2180 
NIOSH/00182080 
9 
8 
1485-1491 
English 
3135957 
WOS:A1988P490600027 
The role of cytochrome-P450 isozymes in the regioselective metabolism of 7,12-dimethylbenz(a)anthracene (57976) (DMBA) by liver microsomes was studied in-vitro. Hepatic microsomes were prepared from female Long-Evans-rats that had been pretreated with phenobarbital or Sudan-III or untreated. These were incubated with tritium labeled DMBA in the presence or absence of metyrapone (54364) for up to 120 minutes. The rates of metabolism to DMBA diols were determined by withdrawing aliquots at various times and analyzing them by high performance liquid chromatography. The formation of the 3,4-diol (the proximate carcinogen) and the 5,6-diol was increased by phenobarbital pretreatment. The formation of the 3,4-diol was suppressed by Sudan-III; the formation of the 5,6-diol and the 8,9-diol was increased. The rate of formation of the diols was no affected by metryapone, except in microsomes pretreated with phenobarbital. Antibodies against specific isoenzymes were used to identify cytochrome-P-450 isoenzymes involved in the regioselective formation of DMBA diols. The authors suggest that adduct formation in microsomes from Sudan-III pretreated rats probably involves epoxide metabolites. Microsomes from phenobarbital pretreated rats probably involve secondary metabolites that may be formed by the cytochrome-P450-PB3 isozyme.