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Marked Differences in the Carcinogenic Activity of Optically Pure (+)- and (-)-trans-7,8-Dihydroxy-7,8-dihydrobenzo(a)pyrene in Newborn Mice

Department of Biochemistry and Drug Metabolism, Hoffmann-LaRoche Inc., Nutley, New Jersey 07110 [J. K., P. G. W., W. L., A. H. C.]; Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218 [H. A., M. K.]; and Section on Oxidation Mechanisms, Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, NIH, Bethesda, Maryland 20014 [H. Y., D. R. T., D. M. J.]

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 weeks of age. Control mice had 0.10 pulmonary adenoma per mouse, whereas animals treated with (+)-BP 7,8-dihydrodiol and (-)-BP 7,8-dihydrodiol had 0.16 and 9.28 pulmonary adenomas per 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 per mouse and (-)-BP 7,8-dihydrodiol caused 32.2 pulmonary adenomas per 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 per mouse, respectively, were observed when the mice were 17 weeks 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.

¹ Present address: Department of Pharmacology, Hadassah-Hebrew University Medical School, Jerusalem, Israel.

² Present address: Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42nd and Dewey Ave., Omaha, Neb. 68105.

³ To whom requests for reprints should be addressed.

Received 4/14/78. Accepted 5/18/78.

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