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Skin Tumor-initiating Activities of the Twelve Isomeric Phenols of Benzo(a)pyrene¹

Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 [T. J. S., W. M. B., S. D.]; Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110 [W. L., A. H. C.]; and Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, NIH, Bethesda, Maryland 20014 [H. Y., D. M. J.]

The skin tumor-initiating activities of the 12 isomeric phenols of benzo(a)pyrene (BP) were determined in mice by use of a two-stage system of tumorigenesis. 11-Hydroxybenzo(a)pyrene was moderately active, whereas 2-hydroxybenzo(a)pyrene and BP were strong tumor initiators when applied topically to CD-1 mice and followed by twice-weekly applications of the promoter 12-O-tetradecanoylphorbol-13-acetate. 1-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, and 12-hydroxybenzo(a)pyrene had less than 5% of the tumor-initiating activity of BP when the data were expressed as papillomas per mouse. After 30 weeks of promotion, the number of papillomas per mouse was 8.4, 8.5, and 2.8, respectively, for the animals treated with BP, 2-hydroxybenzo(a)pyrene, and 11-hydroxybenzo(a)pyrene. A 5-week latency period before the appearance of the first tumor was observed after the application of either 2-hydroxybenzo(a)pyrene or BP, whereas a slightly longer latency period of 7 weeks was observed following application of 11-hydroxybenzo(a)pyrene. The time required for 50% of the animals to develop tumors was 13 weeks for animals treated with BP and 15 weeks for animals treated with 2- or 11-hydroxybenzo(a)pyrene.

¹ This research was supported in part by NIH Grant CA-20076 and by the Energy Research and Development Administration under contract with the Union Carbide Corporation.

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² To whom requests for reprints should be addressed, at Biology Division, Oak Ridge National Laboratory, Post Office Box Y, Oak Ridge, Tenn. 37830.

Received 9/ 6/77. Accepted 12/ 8/77.