Wood A W, Chang R L, Levin W, Ryan D E, Thomas P E, Lehr R E, Kumar S, Sardella D J, Boger E, Yagi H, Sayer J M, Jerina D M, Conney A H
Cancer Res. 1981 Jul;41(7):2589-97.
The mutagenic activities of dibenzo(a,h)(pyrene, dibenzo(a,i)pyrene, and a total of 11 of their benzo-ring derivatives were evaluated in bacterial and mammalian cells in the absence or presence of a mammalian metabolic activation system. trans-1,2-Dihydroxy-1,2-dihydrodibenzo(a,h)pyrene and trans-3,4-dihydroxy-3,4-dihydrodibenzo(a,i)pyrene, the expected dihydrodiol precursors of bay-region diol-epoxides, were metabolized to products which were more mutagenic to strains TA98 and TA100 of Salmonella typhimurium than were the metabolic products formed from their respective parent hydrocarbons. For each dihydrodiol, replacement of the benzo-ring double bond adjacent to the diol moiety with a single bond resulted in tetrahydrodiol derivatives which could not be metabolically activated, suggesting that one or both diastereomeric bay-region diol-epoxides were the bioactivated metabolites. The authentic bay-region diol-epoxide diastereomers of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene in which the benzylic hydroxyl group and the epoxide oxygen are trans (diol-epoxide 2 series) were highly mutagenic in strains TA98 and TA100 of S. typhimurium and in cultured Chinese hamster V79 cells. Neither diol-epoxide was significantly, if at all, metabolized by epoxide hydrolase. The bay-region diol-epoxide of dibenzo(a,i)pyrene was from 1.5 to 5 times more active as a mutagen than the diol-epoxide of dibenzo(a,h)pyrene, and in strain TA98 of S. typhimurium as well as Chinese hamster V79 cells, it had activity comparable to that of the highly carcinogenic bay-region diol-epoxide of benzo(a)pyrene.
在不存在或存在哺乳动物代谢活化系统的情况下，评估了二苯并(a,h)芘、二苯并(a,i)芘及其总共11种苯环衍生物的诱变性。反式-1,2-二羟基-1,2-二氢二苯并(a,h)芘和反式-3,4-二羟基-3,4-二氢二苯并(a,i)芘，即预期的湾区二醇环氧化物的二氢二醇前体，被代谢为对鼠伤寒沙门氏菌TA98和TA100菌株诱变性更强的产物，比由其各自母体烃形成的代谢产物更强。对于每种二氢二醇，将二醇部分相邻的苯环双键替换为单键会产生无法被代谢活化的四氢二醇衍生物，这表明一种或两种非对映异构体的湾区二醇环氧化物是生物活化代谢物。二苯并(a,h)芘和二苯并(a,i)芘的真正湾区二醇环氧化物非对映异构体，其中苄基羟基和环氧基氧是反式的（二醇环氧化物2系列），在鼠伤寒沙门氏菌TA98和TA100菌株以及培养的中国仓鼠V79细胞中具有高度诱变性。两种二醇环氧化物均未被环氧化物水解酶显著代谢（如果有代谢的话）。二苯并(a,i)芘的湾区二醇环氧化物作为诱变剂的活性比二苯并(a,h)芘的二醇环氧化物高1.5至5倍，并且在鼠伤寒沙门氏菌TA98菌株以及中国仓鼠V79细胞中，其活性与高度致癌的苯并(a)芘的湾区二醇环氧化物相当。
