Tumorigenicity of the diastereomeric bay-region benzo(e)pyrene 9,10-diol-11,12-epoxides in newborn mice

Abstract

The tumorigenic activities of benzo(e)pyrene, 9,10-dihydrobenzo(e)pyrene, 9,10-epoxy-9,10,11,12-tetrahydrobenzo(e)-pyrene, the diastereomeric bay-region 9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrenes, and the K-region benzo(e)pyrene 4,5-oxide were assessed in newborn mice, Swiss-Webster mice received a total dose of 0.7 mumol of compound divided into three i.p. injections of 0.1, 0.2, and 0.4 mumol on the first, eighth, and 15th days of life, respectively. 9,10-Epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene was highly toxic to the newborn mice, and the first injection of 0.1 mumol of this benzo(e)pyrene derivative killed all the mice within two weeks. The total dose of 9,10-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene was therefore reduced to 0.07 mumol in divided doses of 0.01, 0.02, and 0.04 mumol. When the animals were killed at 39 to 43 weeks of age, one of the diastereomeric bay-region diol-epoxides, (+/-)-9 beta, 10 alpha-dihydroxy-11 beta, 12 beta-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene, produced a small but significant increase in pulmonary tumors in male mice but had no significant hepatotumorigenic activity. The diastereomerically related diol-epoxide. (+/-)-9 beta, 10 alpha-dihydroxy-11 alpha, 12 alpha-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene, produced a significant incidence of hepatic tumors but had no effect on the formation of pulmonary tumors. Benzo(e)pyrene and the other benzo(e)pyrene derivatives were all nontumorigenic at the doses tested.