Wood A W, Wislocki P G, Chang R L, Levin W, Lu A Y, Yagi J, Hernandez O, Herina D M, Conney A H
Cancer Res. 1976 Sep;36(9 pt.1):3358-66.
Four benzo-ring epoxides of the environmental carcinogen benzo(a)pyrene (BP) were tested for mutagenic and cytotoxic activity in 3 strains of Salmonella typhimurium (TA1538, TA98, and TA100) and in Chinese hamster V79 cells. Although very unstable in aqueous solution, 7beta,8alpha-dihydroxy-0beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol epoxide 1), with the 7-hydroxyl group on the same face of the molecule as the epoxide oxygen, was 1.5 to 4 times as mutagenic in the bacterial strains as was its more stable stereoisomer 7beta,8alpha-dihydroxy-9alpha,10beta-epoxy-7,8,9.10-tetrahydrobenzo(a)pyrene (diol epoxide 2). In V79 cells, diol epoxide 1 had one-third the mutagenic activity of diol epoxide 2 but was at least 10 times more labile than diol epoxide 2 in the tissue culture medium. The half-life of diol epoxide 1 in tissue culture medium was about 30 sec, whereas the half-life of diol epoxide 2 was between 6 and 12 min. 9,10-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, which is saturated in the benzo ring, is also very unstable and has mutagenic activity equal to or greater than diol epoxide 1 in the bacterial and mammalian cells. 7,8-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was more stable in aqueous solution than any of the 9,10-epoxides of BP but was much less mutagenic in both the bacterial and mammalian cells. In v79 cells, diol epoxides 1 and 2 and 9,10-opoxy-7,8,9,10-tetrahydrobenzo(a)pyrene were more than 40 times more cytotoxic than 7,8-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. The mutagenicity of the 2 tetrahydro epoxides toward strain TA98 of S. typhimurium was readily abolished by purified epoxide hydrase, whereas the mutagenic activity of the 2 diol epoxides was relatively unaffected by coincubation with the enzyme.
对环境致癌物苯并(a)芘（BP）的四种苯环环氧化物进行了鼠伤寒沙门氏菌（TA1538、TA98和TA100）3个菌株以及中国仓鼠V79细胞的致突变和细胞毒性活性测试。尽管7β,8α-二羟基-0β,10β-环氧-7,8,9,10-四氢苯并(a)芘（二醇环氧化物1）在水溶液中非常不稳定，但其7-羟基与环氧化物氧在分子的同一面上，在细菌菌株中的致突变性是其更稳定的立体异构体7β,8α-二羟基-9α,10β-环氧-7,8,9,10-四氢苯并(a)芘（二醇环氧化物2）的1.5至4倍。在V79细胞中，二醇环氧化物1的致突变活性是二醇环氧化物2的三分之一，但在组织培养基中的稳定性至少比二醇环氧化物2低10倍。二醇环氧化物1在组织培养基中的半衰期约为30秒，而二醇环氧化物2的半衰期在6至12分钟之间。苯环饱和的9,10-环氧-7,8,9,10-四氢苯并(a)芘也非常不稳定，在细菌和哺乳动物细胞中的致突变活性等于或大于二醇环氧化物1。7,8-环氧-7,8,9,10-四氢苯并(a)芘在水溶液中比BP的任何一种9,10-环氧化物都更稳定，但在细菌和哺乳动物细胞中的致突变性都要低得多。在V79细胞中，二醇环氧化物1和2以及9,10-环氧-7,8,9,10-四氢苯并(a)芘的细胞毒性比7,8-环氧-7,8,9,10-四氢苯并(a)芘高40多倍。两种四氢环氧化物对鼠伤寒沙门氏菌TA98菌株的致突变性很容易被纯化的环氧化物水合酶消除，而两种二醇环氧化物的致突变活性与该酶共同孵育时相对不受影响。
