Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1989-10-10
pubmed:abstractText
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 intensified by the presence of dimethylnitrosamine in the drinking water. Recovery from lysine restriction with respect to MT levels was achieved within 2 days. In lung, moderate effects on MT levels were observed when dietary lysine restriction was combined with the highest dosage of dimethylnitrosamine used (1.2 mg/kg body weight/day). The data strongly emphasize the importance of an adequate amino acid mixture in the diet, to support protein synthesis and to allow for high MT levels and repair of DNA lesions at the O-6 position of guanine during the exposure of the animals to alkylating agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
218
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
135-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Combined effect of dimethylnitrosamine and a lysine-restricted diet on O6-methylguanine-DNA methyltransferase levels in mouse tissues.
pubmed:affiliation
Wenner-Gren Institute for Experimental Biology, University of Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't