Methylation of liver DNA of rat and mouse by N-nitrosodimethylamine formed in vivo from dimethylamine and nitrite.
The extent of formation of N-nitrosodimethylamine (NDMA) in the stomachs of rats and mice after simultaneous oral administration of [14C]dimethylamine and potassium nitrite was determined by measuring the methylation of liver DNA. With doses of around 1 mg dimethylamine hydrochloride/kg body weight and 50 mg potassium nitrite/kg body weight, 0.8% of the amine was nitrosated on average. The individual fluctuations ranged from 0.2 to 1.3% in the rat and from 0.2 to 1.9% in the mouse. Simultaneous administration of 50 mg sodium ascorbate (vitamin C)/kg body weight inhibited the nitrosation by about 80% while 50 mg alpha-tocopherol acetate (vitamin E)/kg body weight reduced the nitrosation by about a half. Assuming similar kinetics and conditions of nitrosation in rats and man, a comparison of the formation of NDMA in vivo from dietary dimethylamine and nitrite with the estimated human uptake of preformed NDMA revealed that in vivo formation in the stomach of man is probably negligible.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004123:Dimethylamines / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice; D009573:Nitrites / Q000378:metabolism*; D051381:Rats; D014810:Vitamin E / Q000494:pharmacology
D004123:Dimethylamines; D009573:Nitrites; D014810:Vitamin E; D004247:DNA; D004128:Dimethylnitrosamine; D001205:Ascorbic Acid