Chemical interaction of disulfiram with nitrosodimethylamine after in vitro enzymatic activation

Abstract
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. HPLC [high performance liquid chromatography] analysis and liquid scintillation measurement provided evidence for the formation of methyldiethyldithiocarbamate (MeDDTC) as a product of the reaction between diethyldithiocarbamate, the main active metabolite of DSF and the methyl-cation released by NDMA after enzymatic activation. The amount of MeDDTC found 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.

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