[Vitamin A and enzyme systems of metabolic activation of genotoxic compounds]

The study was undertaken to study the effects of N-nitrosodimethylamine (NDMA) on the formation of single-strand DNA breaks and gamma-glutamyltransferase-positive knots, the status of the enzymatic systems involved in NDMA metabolism and some other biochemical parameters when rats were on retinol-deficient diets and when they were given excessive vitamin A. The action of retinol on NDMA effects were analyzed by evaluating the activity of glutathione-S-transferase (EC 2.5.1.18), glutathione-reductase (EC 1.2.1.1), aldehyde-dehydrogenase and aldehyde-oxidase (EC 1.2.1.3 and EC 1.2.3.1, respectively), p-450 reductase NADPH cytochrome (EC 1.6.2.4), the demethylase and hydroxylase activities, levels of malonic dialdehyde and the rate of ascorbate-dependent lipid peroxidation, the contents of proteins, phospholipids, cysteine, redox glutathione, glucuronides, sulfates. The level of vitamin A in the animals was found to substantially affect the magnitude of the genotoxic action of NDMA. The supplementary administration of vitamin A reduced the effect of the carcinogen. The mechanism of protective action of retinol was largely explained by the mediated activity of cytochrome-P-450 and glutathione-dependent systems involved in the biotransformation of NDMA. Based on the data available in the literature and their own data, the authors analyzed the effects of retinol on the metabolism of genotoxicants and described possible mechanisms of its antimutagenic and anticarcinogenic action. It is concluded that the effective protection of the body from unfavourable environmental influences may be provided only by supplementary (more than the optimum) intake of vitamin A against the background of a damaging factor.