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Stimulatory Effect of Polycyclic Hydrocarbons and Aromatic Azo Derivatives on the Metabolism of 7,12-Dimethylbenz()anthracene¹

The Wellcome Research Laboratories, Burroughs Wellcome & Co. (U.S.A.), Inc., Tuckahoe, New York 10707

Treatment of rats with certain polycyclic aromatic hydrocarbons and aromatic azo derivatives enhances severalfold the hepatic metabolism of 7, 12-dimethylbenz()anthracene (DMBA) to fluorescent metabolites. Studies with tritiated DMBA revealed that treatment of rats with 3-methylcholanthrene (MC) stimulates the hepatic metabolism of DMBA to 7-hydroxymethyl-12-methylbenz()anthracene (7-OHM-12-MBA), 12-hydroxymethyl-7-methylbenz()anthracene (12-OHM-7-MBA), and several unidentified polar metabolites. MC treatment also enhances the hepatic metabolism of monohydroxymethyl DMBA to highly polar unidentified compounds. The stimulatory effect of MC on the hepatic metabolism of DMBA and its monohydroxymethyl metabolites is paralleled by altered in vivo metabolism of DMBA. Treatment of rats with MC at 24 hours prior to DMBA-³H administration resulted in a markedly decreased concentration of tritiated hydrocarbon in the adrenal gland, mammary gland, and fat. More detailed examination of the adrenal gland and fat revealed that MC pretreatment decreased the concentrations of DMBA, 7-OHM-12-MBA, and 12-OHM-7-MBA in these tissues. The results obtained suggest that the induction of hepatic enzymes that metabolize DMBA and its monohydroxymethyl metabolites play an important role in decreasing the adrenal toxicity and carcinogenicity of DMBA in rats pretreated with polycyclic hydrocarbons and aromatic azo derivatives.

¹ This study was supported by Research Contract No. PH 43-65-1066 from the Pharmacology-Toxicology Programs, NIGMS, NIH.

Received 2/ 1/67. Accepted 6/15/67.