Effects of disulfiram on the metabolism of nitrosodiethylamine during liver carcinogenesis.
We have studied the effects of disulfiram (DSF) administration on the metabolism of nitrosodiethylamine (NDEA) in rats during acute and chronic administration. DSF was found to have the following effects during the course of carcinogenesis: (a) marked decrease in the exhalation of 14CO2 derived from 14C-NDEA; (b) reduction of the total levels of DNA and RNA ethylation in the liver. In acute experiments DSF caused an increase in the amount of NDEA in organs and in the urine. We suggest that inhibition of NDEA biotransformation and the subsequent decrease in the total level of DNA ethylation may prevent specific chemical interactions relevant to carcinogenesis.
D000478:Alkylation; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000652:urine; D004221:Disulfiram / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008168:Lung / Q000378:metabolism; D008297:Male; D009602:Nitrosamines / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution / Q000187:drug effects
D009602:Nitrosamines; D004052:Diethylnitrosamine; D012313:RNA; D004247:DNA; D004221:Disulfiram