Source:http://linkedlifedata.com/resource/pubmed/id/10767627
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2-3
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pubmed:dateCreated |
2000-6-16
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pubmed:abstractText |
Gene-disruption studies involving poly(ADP-ribose) polymerase (Parp) have identified the various roles of Parp in cellular responses to DNA damage. The partial rescue of V[D]J recombination process in SCID/Parp(-/-) double mutant mice indicates the participation of Parp in the repair of DNA strand break. Parp(-/-) mice are more sensitive to the lethal effects of alkylating agents. Parp is also thought to be involved in base-excision repair after DNA damage caused by alkylating agents. On the other hand, resistance of Parp(-/-) mice to DNA damage induced by reactive oxygen species implicates the contribution of Parp to cell death through NAD depletion. Parp(-/-) mice with two different genetic backgrounds also show enhanced sensitivity to the lethal effects of gamma-irradiation. Parp(-/-) mice show more severe villous atrophy of the small intestine compared to the wild-type counterpart in a genetic background of 129Sv/C57BL6. Other forms of enhanced tissue damage have been identified in Parp(-/-) mice with a genetic background of 129Sv/ICR. For example, Parp(-/-) mice exhibit extensive hemorrhage in the glandular stomach and other tissues, such as the testes, after gamma-irradiation. Severe myelosuppression is also observed in both Parp(+/+) and Parp(-/-) mice, but Parp(+/+) mice show extensive extramedullary hematopoiesis in the spleen during the recovery phase of post-irradiation, whereas the spleen of Parp(-/-) mice exhibits severe atrophy with no extramedullary hematopoiesis. The absence of extramedullary hematopoiesis in the spleen is probably the underlying mechanism of hemorrhagic tendency in various tissues of Parp(-/-) mice. These findings suggest that loss of Parp activity could contribute to post-irradiation tissue hemorrhage.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkylating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Methyl Methanesulfonate,
http://linkedlifedata.com/resource/pubmed/chemical/Methylnitrosourea,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-5107
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
462
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
159-66
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10767627-Alkylating Agents,
pubmed-meshheading:10767627-Animals,
pubmed-meshheading:10767627-Cell Death,
pubmed-meshheading:10767627-DNA,
pubmed-meshheading:10767627-DNA Damage,
pubmed-meshheading:10767627-DNA Repair,
pubmed-meshheading:10767627-Male,
pubmed-meshheading:10767627-Methyl Methanesulfonate,
pubmed-meshheading:10767627-Methylnitrosourea,
pubmed-meshheading:10767627-Mice,
pubmed-meshheading:10767627-Mice, Inbred C57BL,
pubmed-meshheading:10767627-Mice, Inbred ICR,
pubmed-meshheading:10767627-Mice, Inbred Strains,
pubmed-meshheading:10767627-Mice, Knockout,
pubmed-meshheading:10767627-Mice, SCID,
pubmed-meshheading:10767627-Mutation,
pubmed-meshheading:10767627-NAD,
pubmed-meshheading:10767627-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:10767627-Spleen,
pubmed-meshheading:10767627-Stomach,
pubmed-meshheading:10767627-Survival Analysis,
pubmed-meshheading:10767627-Testis
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pubmed:year |
2000
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pubmed:articleTitle |
The response of Parp knockout mice against DNA damaging agents.
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pubmed:affiliation |
Biochemistry Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan. mmasutan@gan2.ncc.go.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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