Biotransformation and bioactivation of 7, 12-dimethylbenz[a]anthracene (7, 12-DMBA)

As the result of rapidly developing technological advances, our understanding of the biotransformation and bioactivation of 7, 12-DMBA has increased markedly in recent years. In terms of the metabolic conversion of this polynuclear aromatic hydrocarbon to reactive mutagen/carcinogens, the "bay region" generalization appears to apply, although the candidacy of a number of other intermediary metabolites as ultimate biologically-active forms still remains viable. Large gaps remain in knowledge concerning the nonoxidative metabolic transformations of 7, 12-DMBA, and these require closing in order to further our understanding of the regulation of mechanics controlling steady-state levels of reactive intermediates. Studies on the photooxidation of the hydrocarbon have allowed a stronger appreciation of its chemical reactivity and instability and promise to help resolve many of the apparently conflicting observations of the past. 7, 12-DMBA remains a highly interesting and valuable tool in investigations of bioactivation processes as they relate to the etiology of several important pathologic conditions, including chemically induced tissue necrosis, mutagenesis, carcinogenesis, teratogenesis, atherogenesis, and, possibly, other pathogenic phenomena as well. It is hoped that this review will serve to benefit research in these areas and hasten the reduction of such pathologic phenomena in our society.