The effect of disulfiram on the carcinogenicity of N-butyl-N-(3-carboxypropyl)nitrosamine in the rat.
N-Butyl-N-(3-carboxypropyl)nitrosamine (BCPN) is a proximate carcinogenic metabolite of the bladder specific carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN). The objective of this study was to determine if disulfiram would inhibit the induction of bladder cancer in rats given BCPN, as reported for BHBN (Cancer Res., 39, 3040, 1979). Two groups of 30 male Wistar rats were given 1.5 mM BCPN (0.028%) in the drinking water for 12 weeks. The total dose of BCPN/rat was 5 mmol (0.95 g). During administration of the BCPN, one group of rats was fed a diet containing 0.5% disulfiram, while the other group was maintained on control diet. At the end of 12 weeks, the animals were maintained on control diet without BCPN for an additional 18 weeks, at which time the animals were sacrificed. It was found that 0.5% disulfiram significantly reduced the incidence of bladder cancer, decreasing from 30/30 (100%) in the group receiving BCPN alone to 3/30 (10%) in the group fed the disulfiram diet. The inhibition of BHBN-induced bladder cancer by disulfiram, previously reported, was also confirmed in these experiments.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004221:Disulfiram / Q000494:pharmacology*; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D009602:Nitrosamines; C006853:butyl(3-carboxypropyl)nitrosamine; D004221:Disulfiram