Levin W, Wood A W, Wislocki P G, Kapitulnik J, Yagi H, Jerina D M, Conney A H
Cancer Res. 1977 Sep;37(9):3356-61.
Benzo(a)pyrene (BP) and several benzo-ring derivatives of BP were tested for carcinogenic activity in mice by topical application of each compound once every 2 weeks for 60 weeks. Chronic treatment of C57BL/6J mice with (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (0.025 to 0.10 micronmole/application) indicated that the dihydrodiol was slightly more active as a complete carcinogen than the parent hydrocarbon BP. 7,8-Dihydroxy-7,8,9,10-tetrahydro-benzo(a)pyrene, a compound related to (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene but which lacks the double bond at position 9,10, was inactive as a carcinogen on mouse skin. These results indicate the importance of the double bond at position 9,10 for the carcinogenic activity of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene. Chronic treatment of mice with -.4 micronmole of the highly mutagenic (+/-)-7,beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, (+/-)-7beta,8alpha-dihydroxy-9beta, 10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, or 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene every 2 weeks for 60 weeks resulted in tumor incidences of 0, 8, and 4%, respectively, whereas BP at this dose caused a 100% tumor incidence. The high reactivity of the three epoxides may account for their inactivity or their weak carcinogenic activity on mouse skin.
通过每2周对小鼠局部涂抹一次各化合物，持续60周，对苯并(a)芘（BP）及其几种苯并环衍生物的致癌活性进行了测试。用(±)-反式-7,8-二羟基-7,8-二氢苯并(a)芘（每次涂抹0.025至0.10微摩尔）对C57BL/6J小鼠进行长期处理表明，该二氢二醇作为完全致癌物的活性略高于母体烃BP。7,8-二羟基-7,8,9,10-四氢苯并(a)芘是一种与(±)-反式-7,8-二羟基-7,8-二氢苯并(a)芘相关但在9,10位缺乏双键的化合物，对小鼠皮肤无致癌活性。这些结果表明9,10位的双键对于(±)-反式-7,8-二羟基-7,8-二氢苯并(a)芘的致癌活性很重要。每2周用0.4微摩尔的高致突变性(±)-7,β,8α-二羟基-9α,10α-环氧-7,8,9,10-四氢苯并(a)芘、(±)-7β,8α-二羟基-9β,10β-环氧-7,8,9,10-四氢苯并(a)芘或9,10-环氧-7,8,9,10-四氢苯并(a)芘对小鼠进行长期处理60周，肿瘤发生率分别为0%、8%和4%，而该剂量的BP导致的肿瘤发生率为100%。这三种环氧化物的高反应性可能解释了它们在小鼠皮肤上无活性或致癌活性较弱的原因。
