Linked Life Data

9426069

Source:http://linkedlifedata.com/resource/pubmed/id/9426069

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-20
pubmed:abstractText
To determine whether loss of mismatch repair (MMR) confers sensitivity to N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (CCNU), the sensitivity of MMR-defective (MMR-) variants was compared to that of their parental cells. Loss of MMR confers between 2- and 5-fold hypersensitivity to CCNU on HeLa, Raji, or Chinese hamster ovary cells. We also examined whether the sensitivity to CCNU is a general feature of MMR-human tumor cells. The majority expressed O6-methylguanine-DNA-methyltransferase (MGMT; Mex+ phenotype) that confers resistance to CCNU independent of their MMR status. The single Mex- MMR- SW48 cells were 4-fold more sensitive to CCNU than the Mex- MMR+ SW620 cells. CCNU sensitivity of the Mex+ cells was analyzed after treatment with the MGMT inhibitor O6-benzylguanine. The MMR- AN3CA, LS174T, LoVo, and DU145 cells were 1.4-4.3-fold more sensitive to CCNU than the MMR+ HeLaS3, HT29, and A2780 cells. Hypersensitivity to CCNU was not seen in the MMR- cell lines DLD1, HEC1A, and HCT116, suggesting that other parameters, besides the MGMT and MMR defects, affect the cell's response to this drug. In contrast, loss of MMR was always associated with tolerance to the methylating agent N-methyl-N-nitrosourea. The sensitivity to CCNU in MMR- cells suggests a possible involvement of this repair pathway in repairing interstrand cross-links and may have implications for clinical treatment of MMR- tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
135-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea sensitivity in mismatch repair-defective human cells.
pubmed:affiliation
Istituto Superiore di Sanità, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't