FORMATION OF BENZYLIC ALCOHOLS AND MESO-ALDEHYDES BY ONE-ELECTRON OXIDATION OF DMBA, A MODEL FOR THE FIRST METABOLIC STEP IN METHYLATED CARCINOGENIC HYDROCARBON ACTIVATION

Abstract

The hypothesis that hydroxylation of the 7-methyl group is the first step in metabolic activation of 7,12-dimethylbenz[a]anthracene (DMBA) was advanced over three decades ago (1, 2). A considerable body of evidence supports the hypothesis (3). A chemical model for the oxidative metabolism of DMBA may be useful in understanding the mechanism of metabolic activation of DMBA and other methylated carcinogenic hydrocarbons, particularly the first step. Here we show that a nonenzymatic one-electron oxidation pathway transforms DMBA to carcinogenic alcohol and meso-aldehyde metabolites. The results are consistent with the hypothesis that hydroxylation of the 7-methyl and/or 12-methyl groups is the first metabolic step in DMBA activation. The hypothesis predicts that hydroxylation of other meso-methyl-substituted hydrocarbons is the first essential step in the metabolic activation of methylated carcinogenic hydrocarbons.

Keywords:

• benzylic alcohols
• DMBA
• meso-aldehydes
• one-electron oxidation

Acknowledgments

The authors are indebted to National Institutes of Health/National Cancer Institute for generous financial support (Grant no. CA85134).