O6-methylguanine-DNA methyltransferase and alkylation of liver DNA in mice exposed to dimethylnitrosamine during dietary deficiency of essential amino acids.
Male NMRI mice were fed a diet containing a complete mixture of amino acids or a mixture deficient in methionine-cysteine or lysine (30% of the control level) for a period of 6 days. During the feeding period all mice received dimethylnitrosamine in the drinking water ad libitum. The exposure averaged 1 mg dimethylnitrosamine/kg body weight and day. The concentration of O6-methylguanine-DNA methyltransferase was measured in liver extracts. It decreased significantly in the methionine-cysteine deficient mice. When DNA from the liver was analyzed for alkylated purine bases the mice received a single dose of 14C-labeled dimethylnitrosamine (0.5 or 1 mg/kg body weight) at 120 min before sacrifice. The concentration of O6-methylguanine increased significantly over the control level upon feeding the deficient diets and was restored to the concentration of the controls by refeeding lysine for 2 days following 6 days of lysine deficiency. The increased ratio of O6-methylguanine to N-7-methylguanine indicated that methylation of guanine in the N-7 position was not subject to variation by the intake of dimethylnitrosamine during the dietary deficiencies. The results demonstrate the requirement for a balanced composition of amino acids in the diet to maintain a sufficient concentration of O6-methylguanine-DNA methyltransferase in the cells and thus to permit efficient removal of the methyl group from the O-6 position of guanine in DNA after exposure to dimethylnitrosamine.
D000596:Amino Acids / Q000172:deficiency*; D000818:Animals; D003545:Cysteine / Q000172:deficiency; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004032:Diet; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008239:Lysine / Q000172:deficiency; D008715:Methionine / Q000172:deficiency; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D019853:O(6)-Methylguanine-DNA Methyltransferase
D000596:Amino Acids; D004247:DNA; D008715:Methionine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D008239:Lysine; D003545:Cysteine; D004128:Dimethylnitrosamine