Highly tumorigenic bay-region diol epoxides from the weak carcinogen benzo[c]phenanthrene.
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.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D009154:Mutation; D010616:Phenanthrenes / Q000378:metabolism*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D002273:Carcinogens; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009153:Mutagens; D010616:Phenanthrenes; C026153:benzo(c)phenanthrene 3,4-dihydrodiol; C002615:benzo(c)phenanthrene