Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

Abstract

The tumorigenicities of benzo[a]pyrene and each optical enantiomer of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides derived from trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene were tested by sequential i.p. injection of mice with 1, 2 and 4 nmol or with 2, 4 and 8 nmol of each compound on the 1st, 8th and 15th day of life, respectively. The experiment was terminated when the animals were 34-37 wk old. (+)-7.beta.,8.alpha.-Dihydroxy-9.alpha.,10.alpha.-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-BP-7.beta.,8.alpha.-diol-9.alpha.,10.alpha.-epoxide 2] had exceptional tumorigenicity whereas benzo[a]pyrene and the other 3 optically pure isomers of the benzo[a]pyrene 7,8,-diol-9,10-epoxides had little or no activity. Differences in the carcinogenic activities of optically active isomers of a polycyclic hydrocarbon diol epoxide are demonstrated. Of control mice 11% had pulmonary tumors whereas 71% and 100% of the mice treated with a total dose of 7 or 14 nmol of (+)-BP-7.beta.,8.alpha.-diol-9.alpha.,10.alpha.-epoxide 2, respectively, had pulmonary tumors. Control mice had an average of 0.12 pulmonary tumors per mouse whereas mice treated with a total dose of 7 or 14 nmol of (+)-BP-7.beta.,8.alpha.-diol-9.alpha.,10.alpha.-epoxide 2 had 1.72 and 7.67 pulmonary tumors per mouse, respectively. Mice treated with 14 nmol of (-)-BP-7.alpha.,8.beta.-diol-9.beta.,10.beta.-epoxide 2, (-)-BP-7.beta.,8.alpha.-diol-9.beta.,10.beta.-epoxide 1 or (+)-BP-7.alpha.,8.beta.-diol-9.alpha.,10.alpha.-epoxide 1 had 0.13, 0.25 and 0.34 pulmonary tumors per animal, respectively.