Dimethylnitrosamine demethylation

Lotlikar PD, Baldy WJ Jr, Dwyer EN. 1975. Dimethylnitrosamine demethylation by reconstituted liver microsomal cytochrome P-450 enzyme system. Biochem J 152 705-708. 

The carcinogenicity of dimethylnitrosamine and 4-nitrosomorpholine was reduced by deuterium substitution for hydrogen on carbon atoms alpha to the amino nitrogen.81 82 Consistent with the hypothesis that alpha-carbon oxidation is required for reactive metabolite formation from nitrosamines, there is a substantial primary deuterium isotope effect (ku/kg = 3.8) on the rate of dimethylnitrosamine N-demethylation. 3 Specific deuteration of 3-methylcholanthrene, a potent polycyclic hydrocarbon carcinogen, showed that oxidation of the 1-carbon atom is critical in the tumor-initiating process in mouse skin. ... 

Lotlikar PD, Hong YS, Baldy WS Jr. 1978. Effect of dimethylnitrosamine concentration on its demethylation by liver microsomes from control and 3-methylcholanthrene pretreated rats, hamster and guinea pigs. Cancer Lett 4 355-361. 

One group of substrates of interest is N-nitrosamines, which ru-e carcinogens at many sites and can be formed by chemical reactions within the body (e.g., stomach acid) . Early research on the activation of iV-nitrosodimethylamine (NJf-dimethylnitrosamine) indicated biphasic kinetics of the activating W-demethylation reaction and the possible contribution of multiple P450s and possibly other enzymes The enzjone involved in the low K reaction was shown to be P450 2E1... 

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