This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chou, M. W. Articles by Yang, C. S. Search for Related Content PubMed PubMed Citation Articles by Chou, M. W. Articles by Yang, C. S.

Metabolism of 7,12-Dimethylbenz(a)anthracene and 7-Hydroxymethyl-12-methylbenz(a)anthracene by Rat Liver Nuclei and Microsomes

Department of Pharmacology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20014 [M. W. C., S. K. Y.], and Department of Biochemistry, New Jersey Medical School-College of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103 [W. S., C. S. Y.]

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-MBA) 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) to form hydroxymethyl derivative(s) and at the aromatic ring carbons to form trans-dihydrodiols 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.

¹ Recipient of National Cancer Institute Grant CA-16877.

Received 8/18/80. Accepted 1/13/81.

This article has been cited by other articles:

				M. J. Ronis, J. C. Rowlands, R. Hakkak, and T. M. Badger Inducibility of Hepatic CYP1A Enzymes by 3-Methylcholanthrene and Isosafrole Differs in Male Rats Fed Diets Containing Casein, Soy Protein Isolate or Whey from Conception to Adulthood J. Nutr., April 1, 2001; 131(4): 1180 - 1188. [Abstract] [Full Text]