MARKED DIFFERENCES IN CARCINOGENIC ACTIVITY OF OPTICALLY PURE (+)-AND (-)-TRANS-7,8-DIHYDROXY-7,8-DIHYDROBENZO(A)PYRENE IN NEWBORN MICE

Abstract

Optically pure (+)- and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrenes [(+)- and (-)-BP 7,8-dihydrodiol] were tested for carcinogenicity by giving newborn mice i.p. injections of 20, 40 and 80 nmol of compound on days 1, 8 and 15 of life. The animals were killed at 17 wk of age. Control mice had 0.10 pulmonary adenoma/mouse, whereas animals treated with (+)-BP 7,8-dihydrodiol and (-)-BP 7,8-dihydrodiol had 0.16 and 9.28 pulmonary adenomas/mouse, respectively. When a 5-fold higher dose was administered according to the above dosage schedule, (+)-BP 7,8-dihydrodiol caused 2.34 pulmonary adenomas/mouse and (-)-BP 7,8-dihydrodiol caused 32.2 pulmonary adenomas/mouse. When 200, 400 and 800 nmol of benzo(a)pyrene or (+)-BP 7-8-dihydrodiol were administered sequentially on days 1, 8 and 15 of life, 4.13 and 18.5 pulmonary adenomas/mouse, respectively, were observed when the mice were 17 wk of age. This high dose of (-)-BP 7,8-dihydrodiol killed most of the mice. Administration of (-)-BP 7,8-dihydrodiol caused a high incidence of malignant lymphomas, whereas (+)-BP 7,8-dihydrodiol and benzo(a)pyrene had little or no ability to cause malignant lymphomas.