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 wk for 60 wk. Chronic treatment of C57BL/6J mice with (.+-.)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (0.025-0.10 .mu.mol/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-tetrahydrobenzo(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 0.4 .mu.mol of the highly mutagenic (.+-.)-7.beta.,8.alpha.-dihydroxy-9.alpha.,10.alpha.-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, (.+-.)-7.beta.,8.alpha.-dihydroxy-9.beta.,10.beta.-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene or 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene every 2 wk for 60 wk 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 3 epoxides may account for their inactivity or weak carcinogenic activity on mouse skin.