PMID: 2505067Sep 1, 1989Paper

Combined effect of dimethylnitrosamine and a lysine-restricted diet on O6-methylguanine-DNA methyltransferase levels in mouse tissues

Mutation Research
M KlaudeA von der Decken

Abstract

O6-Methylguanine is a lesion produced in DNA after exposure of animals to the procarcinogen dimethylnitrosamine. The lesion may lead to mutagenesis or carcinogenesis if not repaired. Repair is accomplished by the protein O6-methylguanine-DNA methyltransferase (MT). The methyl group is transferred to a cysteine residue of the protein, which is not regenerated. In mice, after exposure to alkylating agents, the synthesis of the protein is non-inducible. The inactivation of MT as a result of the transmethylation makes new synthesis of the protein molecules necessary for further dealkylation reactions. Protein synthesis activity correlates well with dietary protein quality. Nutritional conditions of amino acid restriction will limit the number of MT molecules synthesized. Continuous exposure of mice to dimethylnitrosamine will further diminish the pool of the protein. In this study, mice were fed a diet low in lysine and simultaneously given dimethylnitrosamine in the drinking water at concentrations resulting in dosages of zero, 0.4 mg or 1.2 mg/kg body weight/day. After 6 days MT was assayed in liver, kidney and lung. In liver and kidney, lysine restriction provoked a decrease in MT levels per mg of tissue DNA which was intensifie...Continue Reading

References

Feb 1, 1985·Chemico-biological Interactions·R Saffhill
Jan 1, 1988·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·M Klaude, A von der Decken
May 1, 1986·Mechanisms of Ageing and Development·M Klaude, A von der Decken
Dec 17, 1985·Biochimica Et Biophysica Acta·R SaffhillP J O'Connor
Jan 1, 1985·The International Journal of Biochemistry·M Norell, A von der Decken
Apr 1, 1973·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A Delpino, U Ferrini
Jan 1, 1974·Nutrition and Metabolism·A von der Decken, P T Omstedt
Jan 1, 1982·Annual Review of Biochemistry·T Lindahl
Jul 10, 1981·Nucleic Acids Research·J M BogdenE Bresnick

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