Induction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95888
Title:
Induction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent.
Authors:
Rafferty, Joseph A; Clarke, A R; Sellappan, D; Koref, M S; Frayling, I M; Margison, Geoffrey P
Abstract:
Expression of both the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) and the p53 tumour suppressor protein are inducible by a number of DNA damaging agents. It is probable that DNA strand breaks are the common inducing signals. This similarity, and the function of p53 as a transcription factor lead us to reason that p53 might be involved in ATase inducibility. We now report that the induction of ATase activity in mouse tissues following gamma-radiation is p53 gene dose dependent. While the extent and kinetics of induction in p53 wildtype mice are consistent with previous reports (a 2-3-fold peak increase at 36 h), no induction is observed in p53 null animals. Importantly the heterozygous mice show an intermediate response but the same kinetics. The basal levels of expression in all tissues examined are unaffected by p53 status. These data represent the first report of a discrete DNA repair function being p53 regulated in vivo and their potential clinical implications are discussed.
Affiliation:
Cancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS Trust), Manchester.
Citation:
Induction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent. 1996, 12 (3):693-7 Oncogene
Journal:
Oncogene
Issue Date:
1-Feb-1996
URI:
http://hdl.handle.net/10541/95888
PubMed ID:
8637727
Type:
Article
Language:
en
ISSN:
0950-9232
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorClarke, A Ren
dc.contributor.authorSellappan, Den
dc.contributor.authorKoref, M Sen
dc.contributor.authorFrayling, I Men
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-04-07T14:03:20Z-
dc.date.available2010-04-07T14:03:20Z-
dc.date.issued1996-02-01-
dc.identifier.citationInduction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent. 1996, 12 (3):693-7 Oncogeneen
dc.identifier.issn0950-9232-
dc.identifier.pmid8637727-
dc.identifier.urihttp://hdl.handle.net/10541/95888-
dc.description.abstractExpression of both the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) and the p53 tumour suppressor protein are inducible by a number of DNA damaging agents. It is probable that DNA strand breaks are the common inducing signals. This similarity, and the function of p53 as a transcription factor lead us to reason that p53 might be involved in ATase inducibility. We now report that the induction of ATase activity in mouse tissues following gamma-radiation is p53 gene dose dependent. While the extent and kinetics of induction in p53 wildtype mice are consistent with previous reports (a 2-3-fold peak increase at 36 h), no induction is observed in p53 null animals. Importantly the heterozygous mice show an intermediate response but the same kinetics. The basal levels of expression in all tissues examined are unaffected by p53 status. These data represent the first report of a discrete DNA repair function being p53 regulated in vivo and their potential clinical implications are discussed.en
dc.language.isoenen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshBrain-
dc.subject.meshCell Cycle-
dc.subject.meshEnzyme Induction-
dc.subject.meshGamma Rays-
dc.subject.meshGene Dosage-
dc.subject.meshGenes, p53-
dc.subject.meshHeterozygote-
dc.subject.meshKidney-
dc.subject.meshKinetics-
dc.subject.meshLiver-
dc.subject.meshLung-
dc.subject.meshMale-
dc.subject.meshMethyltransferases-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Inbred Strains-
dc.subject.meshMice, Knockout-
dc.subject.meshModels, Biological-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshSpecies Specificity-
dc.subject.meshTranscription Factors-
dc.subject.meshTumor Suppressor Protein p53-
dc.subject.meshWhole-Body Irradiation-
dc.titleInduction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS Trust), Manchester.en
dc.identifier.journalOncogeneen

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