title: Carcinogenicity of benzo-ring derivatives of benzo(a)pyrene on mouse skin.
abstract: 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.
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001580:Benzopyrenes / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D004334:Drug Administration Schedule; D004852:Epoxy Compounds / Q000633:toxicity; D005260:Female; D006018:Glycols / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D001580:Benzopyrenes; D002273:Carcinogens; D004852:Epoxy Compounds; D006018:Glycols