Linked Life Data

10964094

Source:http://linkedlifedata.com/resource/pubmed/id/10964094

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-10-2
pubmed:abstractText
O:(6)-methylguanine is responsible for homologous recombination induced by N:-methyl-N:'-nitro-N:-nitrosoguanidine (MNNG) [H. Zhang et al. (1996) CARCINOGENESIS:, 17, 2229]. To test the hypothesis that mismatch repair is causally involved in this process, we generated mismatch repair-deficient strains from a human fibroblast line containing a substrate for detecting intrachromosomal homologous recombination. The four strains selected for study exhibited greatly increased resistance to the cytotoxic effects of MNNG, which was not affected by depletion of O:(6)-alkylguanine-DNA alkyltransferase, and greatly increased sensitivity to the mutagenic effect of MNNG, suggesting that the mutagenic base modifications induced in these four cell strains by MNNG persist in their genomic DNA. Tests showed that their extracts are deficient in the repair of G:T mismatches. The frequency of homologous recombination induced by MNNG in three of these strains was significantly (5-7-fold) lower than that induced in the parental cell strain. This was not the result of a generalized defect in recombination, because when (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epox y-7,8,9, 10-tetrahydrobenzo[a]pyrene was used to induce recombination, all three lines responded with a normal or even a somewhat higher frequency than that observed in the parental strain. The lack of recombination displayed by the fourth strain was shown to result from the loss of part of the recombination substrate. The results strongly suggest that functional mismatch repair is required for MNNG-induced homologous recombination.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1639-46
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Mismatch repair is required for O(6)-methylguanine-induced homologous recombination in human fibroblasts.
pubmed:affiliation
Carcinogenesis Laboratory, Department of Microbiology, Department of Biochemistry and the Genetics Program, Food Safety and Toxicology Building, Michigan State University, East Lansing, MI 48824-1302, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't