Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2000-6-16
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
462
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-66
pubmed:dateRevised
2006-11-15
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
pubmed:year
2000
pubmed:articleTitle
The response of Parp knockout mice against DNA damaging agents.
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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't