Recent Research on Other PAH's Pertaining to the “Bay-Region” Theory

Abstract

The chapter presents studies designed to demonstrate the unique biological activity of the appropriate diol epoxides of several carcinogenic polycyclic aromatic hydrocarbons (PAH's) that have been conducted in an attempt to determine the generality of the bay-region theory and its significance to the PAH-induced chemical carcinogenesis. In the studies, the weak carcinogen, benzo[a]anthracene, that serves as a reasonable model for studies of more potent derivatives such as 7-methylbenzo[a]anthracene, 7,12-dimethylbenzo[a]anthracene, and 3-methylcholanthrene was the first compound to be examined. Perturbational molecular orbital (PMO) calculations were applied and an index assigned to designate the relative mutagenicity and carcinogenicity for a series of positional isomers of the diol epoxide derived from benzo[a]anthracene. The results confirmed that diol epoxide benzo[a]anthracene in which the oxirane ring forms a part of a bay-region is much more active than others that is in accord with the proposed activity series derived from PMO calculations. Earlier studies of the metabolic activation of the five trans dihydrodiols derived from benzo[a]anthracene to mutagens by a highly purified and reconstituted cytochrome P-448 monooxygenase system are also consistent with the bay-region concept. Further, the studies with 5-methylchrysene provide support for the extension of a bay-region theory to methylated compounds.