The effects of ascorbic acid deficiency and excess on the metabolism and toxicity of N-nitrosodimethylamine and N-nitrosodiethylamine in the guinea pig.
The influence of ascorbate deficiency and megadosage on the metabolism of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) was investigated in the guinea pig. After 21 days on a scorbutogenic diet, microsomal cytochrome P-450 and cytochrome b5 levels fell by 51 and 32%, respectively, while cytochrome c reductase activity remained constant. The activities of NDMA and NDEA dealkylase I were also depressed significantly. The Vmax of NDMA demethylase I and NDEA deethylase I was significantly depressed. Also, ascorbate deficiency significantly decreased the plasma clearance of both nitrosamines though the LD50 of neither were altered by ascorbate nutrition. Covalent binding of 14C from [14C]NDMA and [14C]NDEA to DNA obtained from liver slices was significantly lower in the deficient than in the control samples; megadosage appeared to have the opposite effect.
D000818:Animals; D001205:Ascorbic Acid / Q000633:toxicity*; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004052:Diethylnitrosamine / Q000378:metabolism / Q000633:toxicity*; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000633:toxicity*; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009602:Nitrosamines / Q000633:toxicity*
D003573:Cytochrome b Group; D009602:Nitrosamines; D004052:Diethylnitrosamine; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D004128:Dimethylnitrosamine; D001205:Ascorbic Acid