In vitro malignant transformation of mouse fibroblasts by non-K-region dihydrodiols derived from 7-methylbenz(a)anthracene, 7,12-dimethylbenz(a)anthracene, and benzo(a)pyrene.
The 8,9-dihydrodiols of 7-methylbenz(a)anthracene and 7,12-dimethylbenz(a)anthracene and the 7,8-dihydrodiol of benzo(a)pyrene, which are non-K-region diols with adjacent olefinic double bonds that can be metabolized to diol-epoxides, were more active than the parent hydrocarbons in inducing malignant transformation of M2 mouse fibroblasts; a fourth non-K-region diol, the 9,10-dihydrodiol of benzo(a)pyrene was less active than benzo(a)pyrene. The related K-region dihydrodiols, which lack adjacent olefinic double bonds, and 6-hydroxybenzo(a)pyrene were inactive, 7,8-Dihydrobenzo(a)pyrene, a more potent carcinogen than the 9,10 isomer, induced malignant transformation, but the 9,10 isomer was inactive. Transformed cells with abnormal morphology yielded sarcomas on injection into isologous mice; treated but morphologically normal cells did not. These results support the role of diols and diol-epoxides in the metabolic activation of polycyclic hydrocarbons.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000031:analogs & derivatives*; D001580:Benzopyrenes; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006018:Glycols; D051379:Mice; D012513:Sarcoma, Experimental / Q000209:etiology
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D006018:Glycols; D015127:9,10-Dimethyl-1,2-benzanthracene