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Inhibition of N-n-Butyl-N-(4-hydroxybutyl)nitrosamine-induced Urinary Bladder Cancer in Rats by Administration of Disulfiram in the Diet¹

Veterans Administration Medical Center [C. C. I.] and Departments of Pathology [W. M. M.] and Urology [C. C. I., A. J. T.], University of Tennessee Center for the Health Sciences, Memphis, Tennessee 38104

The objective of this study was to determine if disulfiram would influence the induction of urinary bladder cancer in rats given N-n-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN). Adult male Wistar rats were divided into: Group 1, control diet, 30 rats; Group 2, control diet plus 0.025% BHBN in the drinking water, 60 rats; Group 3, control diet containing 0.5% disulfiram, 30 rats; and Group 4, control diet containing 0.5% disulfiram plus 0.025% BHBN in the drinking water, 60 rats. The animals were kept on these regimens for 15 weeks and then were transferred to and maintained on control diet. The average total intake of BHBN was 1.21 g/rat for Group 2 and 1.23 g/rat for Group 4. The cumulative incidences of bladder cancer at 25 weeks after initial exposure to BHBN were: Group 1, 0 of 9; Group 2, 27 of 27; Group 3, 0 of 9; and Group 4, 0 of 27. At termination of the experiment (32 to 42 weeks), the final bladder cancer incidences were: Group 1, 0 of 30 (0%); Group 2, 57 of 57 (100%); Group 3, 0 of 24 (0%); and Group 4, 7 of 55 (13%). Except for a carcinoma of the renal pelvis in one rat in Group 2 and the bladder tumors in Groups 2 and 4, tumors were not detected in other organs of any of these rats. It was concluded that disulfiram significantly inhibited the induction of bladder cancer in rats exposed to BHBN. The mechanism of action of disulfiram in this process is under investigation.

¹ These studies were supported by the United States Veterans Administration and by USPHS Grant CA16765 from the National Cancer Institute through the National Bladder Cancer Project.

² To whom requests for reprints should be addressed, at Veterans Administration Medical Center, 1030 Jefferson Avenue, Memphis, Tenn. 38104.

Received 4/ 2/79. Accepted 5/ 8/79.