Chemical interaction of disulfiram with nitrosodimethylamine after in vitro enzymatic activation
The in vitro reaction between disulfiram (DSF) and N-nitroso(/sup 14/C)dimethylamine ((/sup 14/C)NDMA) was studied. Incubations of DSF with (/sup 14/C)NDMA were carried out in the presence of rat liver microsomes, control 9000 g (S9) supernatant fraction and phenobarbital-induced S9 fraction. HPLC 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 (/sup 14/C)NDMA.
- Research Organization:
- Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg, FRG
- OSTI ID:
- 6965632
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 5:2
- Country of Publication:
- United States
- Language:
- English
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NITROSO COMPOUNDS
METABOLISM
CARBON 14 COMPOUNDS
METABOLIC ACTIVATION
PHENOBARBITAL
TRACER TECHNIQUES
ANESTHETICS
ANTICONVULSANTS
AZINES
BARBITURATES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HETEROCYCLIC COMPOUNDS
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PYRIMIDINES
550501* - Metabolism- Tracer Techniques