Radiosensitization and DNA repair inhibition by pentoxifylline in NIH3T3 p53 transfectants

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dc.contributor.authorBinder A.
dc.contributor.authorTheron T.
dc.contributor.authorDonninger H.
dc.contributor.authorParker M.
dc.contributor.authorBohm L.
dc.date.accessioned2011-05-15T16:16:44Z
dc.date.available2011-05-15T16:16:44Z
dc.date.issued2002
dc.description.abstractPurpose: To examine the role of p53 mutations in the modulation of DNA repair and radiotoxicity by pentoxifylline. Materials and methods: NIH3T3 murine cells transfected with mutant p53 constructs were examined for the influence of pentoxifylline on radiotoxicity to Co60 γ-irradiation by colony assay. DNA repair (0-100Gy) was measured by constant-field gel electrophoresis. Apoptosis was assessed by flow cytometry with the annexin-V-binding assay. Results: In the two p53 hot-spot mutant cell lines p53-S269R and p53- + 15, the SF10 radiotoxicity enhancement factors induced by the pentoxifylline were 8.0 and 9.7, respectively. In the p53 deletion mutant p53-ΔA cell line, the radiotoxicity enhancement factor was 2.6. No radiosensitization was obtained in the untransfected p53 wild-type cell line U-Wt and in the transfected p53 double-wild-type p53-Wt cell line. When pentoxifylline was added after irradiation at the time of maximum G2 block expression, no radiosensitization was observed in any of the five cell lines. Constant-field gel electrophoresis analyses after 20 h of repair showed that pentoxifylline suppresses DNA double-strand break repair in all p53 mutant cell lines, as indicated by repair inhibition factors of 2.0-2.3. No repair suppression was found in the p53 wild-type cell lines. Conclusions: p53 mutations are a general requirement for radiosensitization by pentoxifylline and the level of radiosensitization depends upon the location of the p53 mutation.
dc.description.versionArticle
dc.identifier.citationInternational Journal of Radiation Biology
dc.identifier.citation78
dc.identifier.citation11
dc.identifier.issn09553002
dc.identifier.other10.1080/0955300021000016369
dc.identifier.urihttp://hdl.handle.net/10019.1/13913
dc.subjectcobalt 60
dc.subjectDNA
dc.subjectpentoxifylline
dc.subjectprotein p53
dc.subjectanimal cell
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcell death
dc.subjectcell strain 3T3
dc.subjectcontrolled study
dc.subjectDNA repair
dc.subjectflow cytometry
dc.subjectgamma irradiation
dc.subjectgene mutation
dc.subjectmouse
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectradiosensitization
dc.subject3T3 Cells
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectCell Survival
dc.subjectDNA
dc.subjectDNA Repair
dc.subjectDose-Response Relationship, Radiation
dc.subjectFibroblasts
dc.subjectG2 Phase
dc.subjectGamma Rays
dc.subjectMice
dc.subjectMutagenesis, Site-Directed
dc.subjectPentoxifylline
dc.subjectRadiation Tolerance
dc.subjectRadiation-Protective Agents
dc.subjectTransfection
dc.subjectTumor Suppressor Protein p53
dc.subjectAnimalia
dc.subjectMurinae
dc.titleRadiosensitization and DNA repair inhibition by pentoxifylline in NIH3T3 p53 transfectants
dc.typeArticle
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