Iyer R P, Lyga J W, Secrist J A, Daub G H, Slaga T J
Cancer Res. 1980 Apr;40(4):1073-6.
The abilities of various mono and dimethyl derivatives of benzo(a)pyrene (BP) to initiate skin tumors in mice were determined by using a two-stage system of tumorigenesis. 11-Methylbenzo(a)pyrene was found to be approximately 3 times more active as a tumor initiator than was the parent hydrocarbon; 1-methyl benzo(a)pyrene was about twice as active as was BP. Substitution of a methyl group in positions 7, 8, 9, or 10 of BP, which would be involved in a bay-region diol-epoxide, completely counteracts the tumor-initiating ability of BP. 3-, 4-, and 12-methyl-benzo(a)pyrenes and activity equivalent to that of BP, whereas 2-, 5-, and 6-methylbenzo(a)pyrenes, as well as 1,2-, 4,5-, 1,6-, and 3,6-dimethylbenzo(a)pyrenes, were all less active than BP. The concepts of steric inhibition of metabolic activation and stereospecific activation are suggested to explain the tumor-initiating activities of various methylated derivatives.
通过使用两阶段肿瘤发生系统，测定了苯并(a)芘（BP）的各种单甲基和二甲基衍生物诱发小鼠皮肤肿瘤的能力。发现11-甲基苯并(a)芘作为肿瘤引发剂的活性约为母体碳氢化合物的3倍；1-甲基苯并(a)芘的活性约为BP的两倍。在BP的7、8、9或10位上取代一个甲基（这将参与湾区二醇环氧化物的形成），完全抵消了BP的肿瘤引发能力。3-、4-和12-甲基苯并(a)芘的活性与BP相当，而2-、5-和6-甲基苯并(a)芘以及1,2-、4,5-、1,6-和3,6-二甲基苯并(a)芘的活性均低于BP。提出了空间位阻代谢活化和立体特异性活化的概念来解释各种甲基化衍生物的肿瘤引发活性。
