Marquardt H, Grover P L, Sims P
Cancer Res. 1976 Jun;36(6):2059-64.
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.
7-甲基苯并(a)蒽和7,12-二甲基苯并(a)蒽的8,9-二氢二醇以及苯并(a)芘的7,8-二氢二醇，这些都是具有相邻烯键式双键的非K区二醇，可代谢为二醇环氧化物，它们在诱导M2小鼠成纤维细胞恶性转化方面比母体碳氢化合物更具活性；苯并(a)芘的第四个非K区二醇，即9,10-二氢二醇，其活性低于苯并(a)芘。缺乏相邻烯键式双键的相关K区二氢二醇以及6-羟基苯并(a)芘没有活性，7,8-二氢苯并(a)芘是比9,10异构体更强的致癌物，可诱导恶性转化，但9,10异构体没有活性。形态异常的转化细胞注射到同基因小鼠体内会产生肉瘤；经过处理但形态正常的细胞则不会。这些结果支持了二醇和二醇环氧化物在多环碳氢化合物代谢活化中的作用。
