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Dibenzo[a,e]fluoranthene, its 7-hydroxy, 3,4- and 12,13-dihydrodiol metabolic derivatives as well as three synthetic, structurally related hydrocarbons, were tested for mutagenicity towards Salmonella typhimurium TA100 strain in the presence of 3-methylcholanthrene-treated rat and mouse liver post-mitochondrial supernatants. Of these compounds, the 12,13-dihydrodiol showed the highest activity, being 6-10 times more mutagenic than the parent compound. Our data, in conjunction with those of previous studies on the liver microsomal metabolism and DNA binding of dibenzo[a,e]fluoranthene and its dihydrodiols, indicate that activation of dibenzo[a,e]fluoranthene to bacterial mutagens may occur predominantly through a vicinal, non-bay-region 12,13-dihydrodiol epoxide.

In the four years since its inception, the bay-region theory has proved highly successful in predicting which diol epoxide of a polycyclic aromatic hydrocarbon would have the highest tumorigenic activity. The present studies on benzo[c]phenanthrene have shown this hydrocarbon to be unique. It is the first hydrocarbon for which the bay-region diol epoxide that has its benzylic hydroxyl group and epoxide oxygen cis (isomer-1 series) has significant tumorigenic activity. Additionally, its bay-region diol epoxides are the most tumorigenic diol epoxides yet tested on mouse skin despite their expected and observed very low chemical reactivity. Perhaps some unique feature of the shape of benzo[c]phenanthrene can account for the remarkable biological activity of its bay-region diol epoxides. The high degree of crowding in the bay-region of benzo[c]phenanthrene may be such a contributing factor. It is know, for example, that methyl-substitution in the bay-region but not on the critical benzo-ring enhances the tumorigenic activity of 7,12-dimethylbenzo[a]anthracene relative to 7-methylbenzo[a]anthracene (Newman, 1976), of 5-methylchrysene relative to chrysene (Hecht et al., 1974), and of 11-methylbenzo[a]pyrene relative to benzo[a]pyrene (Iyer et al., 1980). Steric crowding in the bay-region of benzo[c]phenanthrene (Hirshfeld, 1963) and 7,12-dimethylbenzo[a]anthracene has been shown by x-ray crystallography to cause out-of-plane deformation of their aromatic ring systems.