Influence of disulfiram on the organotropy of the carcinogenic effect of dimethylnitrosamine and diethylnitrosamine in rats.
In former studies in rats and mice it was shown that the acute toxicity of dimethylnitrosamine (DMNA) and diethylnitrosamine (DENA) is reduced by additional treatment with tetraethylthiuramdisulfide [(Disulfiram, Antabus (DSF)]. In long-term experiments in 40 rats given 500 mg/kg DSF/week the substance did not show carcinogenic effects, however, influenced the action of the nitrosamines. DENA, which was administered to 38 rats in a dosage of 20 mg/kg/week, induced liver tumors in 90% of the animals; in 29% besides some precancerous stages predominantly malignant carcinomas of the oesophagus were seen. DMNA when given to 31 rats in a dosage of 4 mg/kg/week induced liver tumours in 55% of the animals. 26 rats were treated with a combination of 500 mg/kg DSF/week and 20 mg/kg DENA/week. In only 31% of the animals of this group liver tumors were found, however, 81% of them besides some precancerous stages showed predominantly carcinomas of the oesophagus. The combination of 500 mg/kg DSF/week and 4 mg/kg DMNA/week induced only 1 liver tumor (=3%) out of a group of 29 animals, whereas 59% of them showed squamous cell carcinomas of the paranasal sinus that were not seen when DMNA was given alone.
D000818:Animals; D004052:Diethylnitrosamine / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental; D009602:Nitrosamines / Q000494:pharmacology*; D009928:Organ Specificity / Q000187:drug effects; D010255:Paranasal Sinus Neoplasms / Q000139:chemically induced; D051381:Rats
D009602:Nitrosamines; D004052:Diethylnitrosamine; D004128:Dimethylnitrosamine; D004221:Disulfiram