O6-methylguanine-DNA methyltransferase and alkylation of liver DNA in mice exposed to dimethylnitrosamine during dietary deficiency of essential amino acids.
Mutat Res
; 183(3): 287-94, 1987 May.
Article
em En
| MEDLINE
| ID: mdl-3106802
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
DNA
/
Dimetilnitrosamina
/
Reparo do DNA
/
Aminoácidos
/
Metiltransferases
Limite:
Animals
Idioma:
En
Revista:
Mutat Res
Ano de publicação:
1987
Tipo de documento:
Article