Marked differences in the tumor-initiating activity of optically pure (+)- and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene on mouse skin.
The ability of optically pure (+)- and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to initiate skin tumors in mice was determined with a two-stage tumorigenesis system. A single application of 50 to 200 nmoles of (+)- or (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to the backs of CD-1 mice followed by twice-weekly applications of 12-O-tetradecanoyl-phorbol-13-acetate revealed that the (-)-enantiomer was 5- to 10-fold more potent than was the (+)-enantiomer as a tumor initiator at the three dosage levels tested. When the tumor-initiating activities of the (+)0 and (-)-enantiomers of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene were compared to the activity of benzo(a)pyrene at an equimolar dose, the (-)-enantiomer was more active while the (+)-enantiomer was considerably less active. This is the first report of differences in the carcinogenic activity between optical enantiomers.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced* / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001580:Benzopyrenes; D013755:Tetradecanoylphorbol Acetate