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The Comparative Carcinogenicities of 2-Acetylaminofluorene and Its N-Hydroxy Metabolite in Mice, Hamsters, and Guinea Pigs^*

Elizabeth C. Miller, James A. Miller and Makoto Enomoto

( McArdle Memorial Laboratory for Cancer Research, Medical School, University of Wisconsin, Madison, Wisconsin)

N-Hydroxy-2-acetylaminofluorene (N-hydroxy-AAF), a proximate carcinogenic metabolite of AAF in the rat, produced tumors at sites of local application—i.e., the forestomach (on oral administration) and sites of injection in the mouse and hamster, whereas AAF was inactive at these sites. At other sites—the liver, mammary gland, and urinary bladder in the mouse and the liver in the hamster—AAF and its N-hydroxy metabolite had equal carcinogenic activities. When treated topically with croton oil mice fed AAF had a higher incidence of skin papillomas than did mice fed N-hydroxy-AAF. Both the mouse and hamster N-hydroxylate AAF in vivo. AAF is not carcinogenic in the guinea pig, and no N-hydroxylation of AAF has been detected in this species. However, administration of N-hydroxy-AAF to the guinea pig resulted in adenocarcinomas of the small intestine (upon feeding) and sarcomas (upon injection). The comparative carcinogenicities of AAF and N-hydroxy-AAF in the mouse, hamster, and guinea pig provide further evidence that N-hydroxy-AAF is a proximate carcinogenic metabolite of AAF in those species in which AAF is carcinogenic.

^* This investigation was supported by Grants CA-07175 and CRTY-5002 of the National Cancer Institute, United States Public Health Service; by a grant from the Jane Coffin Childs Memorial Fund for Medical Research; and by the Alexander and Margaret Stewart Trust Fund. We wish to thank Mrs. Joan Craig, Mrs. Nancy Kehm, and Mrs. Diane McKechnie for valuable assistance.

Present address: Department of Pathology, University of Tokyo.

Received 7/27/64.

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