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Prevention by Testosterone of the Intestinal Toxicity Caused by the Antitumor Agent 3-Deazauridine¹

Department of Experimental Therapeutics and J. T. Grace, Jr., Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14203

3-Deazauridine caused a greater increase in the life-span of male than of female DBA/2Ha mice bearing leukemia L1210. The toxicity of the drug, as manifested by weight loss and mortality, was more pronounced in female than in male mice. Castration decreased this toxicity in females but increased it in males. Administration of testosterone, either concomitantly with the drug or in depot form 5 days before drug treatment, prevented or reduced both weight loss and mortality. Histopathological examination showed the intestinal epithelium to be markedly affected by 3-deazauridine, as evidenced by necrosis and the pronounced inhibition of mitotic activity. These effects were alleviated by testosterone.

¹ This study was aided by Grants CA-12585 and CA-13038 from National Cancer Institute, USPHS.

Received 11/19/73. Accepted 2/12/74.