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Inhibition by Cysteamine-HCl of Oncogenesis Induced by 7,12-Dimethylbenz(a)anthracene without Affecting Toxicity¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021

The effects of cysteamine-HCl, a radical scavenger, on 7,12-dimethylbenz(a)anthracene-induced toxicity and oncogenesis were studied in vitro and in vivo. While the addition of cysteamine-HCl to mouse fibroblasts (M2 line) prior to and after the addition of 7,12-dimethylbenz(a)anthracene did not affect the carcinogen-induced toxicity (reduced plating efficiency), the number of transformed foci was markedly reduced. In vivo, the i.p. administration of cysteamine-HCl to Sprague-Dawley rats, prior to and following the injection of 7,12-dimethylbenz(a)anthracene i.v., did not affect the carcinogen-induced adrenal necrosis and lesions of the small intestinal epithelium. Similar treatment did, however, markedly reduce the number of mammary tumors formed. These results suggest that the toxic and oncogenic changes induced by 7,12-dimethylbenz(a)anthracene are due to two different metabolites, and support the concept that the latter effect may be mediated by a radical.

¹ Supported in part by Grants CA 08748 and CA 15205 from the National Cancer Institute, USPHS, and by Grant BC-140 from the American Cancer Society, Inc.

² Performed in partial fulfillment of the requirements for the degree of Doctor of Philosophy from the Graduate School of Medical Sciences, Cornell University.

Received 5/23/74. Accepted 9/ 9/74.