Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-5
pubmed:abstractText
In mice, genetic modification of the gene encoding p53 affects both cancer incidence and longevity. In humans, we recently found that a TP53 codon 72 Arginine (Arg) to Proline (Pro) polymorphism affected both cancer incidence and longevity as well. The TP53 codon 72 polymorphism has previously been shown to influence the apoptotic potential of human cells in response to oxidative stress. Here, we studied the influence of this polymorphism on the cellular responses to X-irradiation of fibroblasts obtained from nonagenarians. We found that the average clonogenic survival after X-irradiation was similar for the three TP53 codon 72 genotype groups. As described before, X-irradiation did not induce an appreciable degree of apoptosis in human fibroblasts. However, percentages of senescence-associated (SA)-beta-galactosidase positive cells (p < 0.001), micronucleated cells (p < 0.001) and cells displaying abnormal nuclear morphologies (p < 0.001) significantly increased with the radiation dose. Compared to Arg/Arg fibroblasts, Pro/Pro fibroblasts exhibited higher irradiation dose-dependent increases in SA-beta-galactosidase positive cells (p(interaction) = 0.018), micronucleated cells (p(interaction) = 0.005) and cells displaying abnormal nuclear morphologies (p(interaction) = 0.029) at 3 days after irradiation. Possibly, these differences in cellular responses to stress between the TP53 codon 72 genotypes contribute to the differences in cancer incidence and longevity observed earlier for these genotypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0047-6374
pubmed:author
pubmed:issnType
Print
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-82
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Influence of the TP53 codon 72 polymorphism on the cellular responses to X-irradiation in fibroblasts from nonagenarians.
pubmed:affiliation
Department of Gerontology and Geriatrics, Leiden University Medical Centre, RC Leiden, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't