Metabolism of 7,12-dimethylbenz(a)anthracene and 7-hydroxymethyl-12-methylbenz(a)anthracene by rat liver and microsomes

• Published in: Cancer research (Chicago, Ill.) Ill.), 1981-04, Vol.41 (4), p.1559
• Main Authors: Chou, M W, Yang, S K, Sydor, W, Yang, C S
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - analogs & derivatives; 9,10-Dimethyl-1,2-benzanthracene - metabolism; Animals; Benz(a)Anthracenes - metabolism; Carcinogens; Cell Nucleus - metabolism; Chemical Phenomena; Chemistry; Chromatography, High Pressure Liquid; Liver - metabolism; Liver - ultrastructure; Male; Methylcholanthrene - pharmacology; Microsomes, Liver - metabolism; Phenobarbital - pharmacology; Rats
• ISSN: 0008-5472

The metabolism of 7,12-[14C]dimethylbenz(a)anthracene ([14C]DMBA) and 7-[7-CH2-3H]hydroxymethyl-12-methylbenz(a)anthracene ([7-CH2-3H]7-OHM-12-BMA) by rat liver nuclei and microsomes was studied by high-performance liquid chromatography. DMBA and 7-OHM-12-MBA are metabolized at methyl group(s) and at the aromatic ring carbons to form trans-dihyrodiols at positions 3, 4, 5, 6, 8, 9, and 10,11 and phenols at positions 2, 3, and 4 by both nuclear and microsomal enzymes. Both nuclear and microsomal monooxygenase enzyme activities were inducible by pretreatment of the animals with phenobarbital or 3-methylcholanthrene. The rates of formation of all metabolites by microsomes were five- to 20-fold higher than those by nuclei in metabolizing DMBA or 7-OHM-12-MBA. The presence of a hydroxyl group at the 7-methyl position of DMBA markedly decreased the rate of metabolism. The rate of total metabolism of 7-OHM-12-MBA was only 20 to 70% of that of DMBA under identical in vitro incubation conditions. The 3-methylcholanthrene- and phenobarbital-induced enzymes showed a significantly different regioselectivity toward the metabolism of DMBA or 7-OHM-12-MBA and are attributed to different forms of cytochrome P-450 present in the enzyme preparations.