MARKED DIFFERENCES IN TUMOR-INITIATING ACTIVITY OF OPTICALLY PURE (+)- AND (-)-TRANS-7,8-DIHYDROXY-7,8-DIHYDROBENZO(A)PYRENE ON MOUSE SKIN

Abstract

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 2 stage tumorigenesis system. A single application of 50-200 nmol of (+)- or (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to the backs of CD-1 mice followed by twice weekly applications of 12-0-tetradecanoyl-phorbol-13-acetate revealed that the (-)-enantiomer was 5- to 10-fold more potent than the (+)-enantiomer as a tumor initiator at the 3 dosage levels tested. When the tumor initiating activities of the (+)- 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 1st report of differences in the carcinogenic activity between optical enantiomers.