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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
1989-6-8
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pubmed:abstractText |
We have selected two N-methyl-N-nitrosourea (MNU)-resistant derivatives of the SV40-transformed, alkyltransferase-deficient (Mex-) human fibroblast cell line MRC5V1. Both derivatives remain Mex-. They are cross-resistant to methylmethanesulphonate (MMS) and 6-thioguanine (6TG) but not 2,6-diaminopurine. They show increased sensitivity to the bifunctional chloroethylating agent mitozolomide (MTZ). We have transfected MRC5V1 and one of our MNU-resistant lines with the bacterial O6-methylguanine (O6-MeG)-DNA methyltransferase (ada) gene. Transfectants of MRC5V1 are significantly more resistant to MNU but exhibit only a small increase in resistance to MMS and MTZ. Transfectants of the MNU-resistant derivative exhibit only a small additional increase in resistance to MNU, no further increase in resistance to MMS and a large increase in resistance to MTZ. The pattern of resistance to cytotoxic agents of these transfectants suggests that a second mechanism of resistance to MNU, independent of alkyltransferase expression, is operating in our resistant lines. This mechanism apparently enables the cells to tolerate O6-MeG and 6TG, but not chloroethyl adducts in their DNA.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0143-3334
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
10
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
893-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:2539916-Carcinogens,
pubmed-meshheading:2539916-Cell Line,
pubmed-meshheading:2539916-Cell Survival,
pubmed-meshheading:2539916-Cell Transformation, Neoplastic,
pubmed-meshheading:2539916-Drug Resistance,
pubmed-meshheading:2539916-Fibroblasts,
pubmed-meshheading:2539916-Humans,
pubmed-meshheading:2539916-Methylnitrosourea,
pubmed-meshheading:2539916-Methyltransferases,
pubmed-meshheading:2539916-O(6)-Methylguanine-DNA Methyltransferase,
pubmed-meshheading:2539916-Plasmids,
pubmed-meshheading:2539916-Simian virus 40,
pubmed-meshheading:2539916-Transfection
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pubmed:year |
1989
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pubmed:articleTitle |
Properties of N-methyl-N-nitrosourea-resistant, Mex- derivatives of an SV40-immortalized human fibroblast cell line.
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pubmed:affiliation |
MRC Cell Mutation Unit, Sussex University, Brighton, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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