Chemical interaction of disulfiram with nitrosodimethylamine after in vitro enzymatic activation.
The in vitro reaction between disulfiram (DSF) and N-nitroso[14C]dimethylamine [( 14C]NDMA) was studied. Incubations of DSF with [14C]NDMA were carried out in the presence of rat liver microsomes, control 9000 g (S9) supernatant fraction and phenobarbital-induced S9 fraction. H.p.l.c. analysis and liquid scintillation measurement provided evidence for the formation of methyldiethyldithiocarbamate (MeDDTC) as a product of the reaction between diethyldithiocarbamate (DDTC), the main active metabolite of DSF and the 'methyl-cation' released by NDMA after enzymatic activation. The amount of MeDDTC found here was consistent with the rate of oxidation of NDMA to formaldehyde. Scintillation counting confirmed that other radioactive peaks, not due to MeDDTC, were unrelated to the methylation of L-cysteine by [14C]NDMA.
D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004128:Dimethylnitrosamine / Q000378:metabolism*; D004221:Disulfiram / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D004128:Dimethylnitrosamine; D004221:Disulfiram