Mechanisms of inhibition by ascorbate of microbial mutagenesis induced by N-nitroso compounds.
Mutagenesis induced by N-methyl-N-nitrosoguanidine (MNNG) and dimethylnitrosamine (DMN) in Salmonella TA 1530 was inhibited by ascorbate. Inhibition of MNNG-induced mutagenesis resulted from a reaction between ascorbate and MNNG that led to consumption of MNNG. The rate of this reaction was considerably enhanced by catalytic amounts of Cu(II) and Fe(III). No direct reaction between DMN and ascorbate was detectable, but relatively high concentrations of Cu(II) enchanced inhibition of DMN-induced mutagenesis by ascorbate. Added protein reduced the effectiveness of Cu(II) as a catalyst of the reaction between ascorbate and MNNG, which suggested that the microsomal protein necessary to activate DMN, may reduce the concentration of free Cu(II) and thereby lower its catalytic efficiency. Mutagenesis by N-methyl-N-nitrosourea was not inhibited by ascorbate.
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008770:Methylnitrosourea / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D009154:Mutation / Q000187:drug effects*; D009602:Nitrosamines / Q000037:antagonists & inhibitors*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D009602:Nitrosamines; D008769:Methylnitronitrosoguanidine; D008770:Methylnitrosourea; D003300:Copper; D007501:Iron; D004128:Dimethylnitrosamine; D001205:Ascorbic Acid