(+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo (a)pyrene: a potent skin carcinogen when applied topically to mice.
(+/-)-trans-7,8-Dihydroxy-7,8-dihydrobenzo[a]-pyrene, a known metabolite of benzo [a]pyrene, has been tested for carcinogenic activity on mouse skin by topical application of 0.15 or 0.30 mumol every 2 weeks for 60 weeks. At the low dose (0.15 mumol), the compound was equipotent to the parent hydrocarbon, benzo[a]pyrene, and considerably more potent than its metabolic precursor, benzo[a]pyrene 7,8-oxide, in eliciting tumors, as determined by both the onset of tumors and the total number of animals developing carcinomas. Application of 7,8-epoxy-,8,9,10-tetrahydrobenzo[a]pyrene (0.30 mumol every 2 weeks), a compound related to the carcinogenic benzo[a]pyrene 7,8-oxide but with the double bond removed from the 9,10-position of the molecule, did not elicit any tumors. The above results indicate that the (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene is a more proximate carcinogen than benzo[a]pyrene 7,8-oxide and that the carcinogenicity of benzo[a]pyrene 7,8-oxide and (+/-)trans-7,8-digydrobenzo[a]pyrene may be due to metabolic conversion of these compounds to the highly reactive and mutagenic stereoisomers of 7,8-digydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D001580:Benzopyrenes