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.

• Authors: W Levin, A W Wood, P G Wislocki, J Kapitulnik, H Yagi, D M Jerina, A H Conney
• Journal: Cancer research (Cancer Res) Vol. 37 Issue 9 Pg. 3356-61 (Sep 1977) ISSN: 0008-5472 [Print] United States
• PMID: 884679 (Publication Type: Journal Article)

Chemical References

• Benzopyrenes
• Carcinogens
• Epoxy Compounds
• Glycols

Topics

• Animals
• Animals, Newborn
• Benzopyrenes (administration & dosage, toxicity)
• Carcinogens
• Chemical Phenomena
• Chemistry
• Drug Administration Schedule
• Epoxy Compounds (toxicity)
• Female
• Glycols (toxicity)
• Mice
• Mice, Inbred C57BL
• Neoplasms, Experimental (chemically induced)
• Skin Neoplasms (chemically induced)
• Structure-Activity Relationship