Radiosensitization and DNA repair inhibition by pentoxifylline in NIH3T3 p53 transfectants
Date
2002
Authors
Binder A.
Theron T.
Donninger H.
Parker M.
Bohm L.
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Journal ISSN
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Abstract
Purpose: 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.
Description
Keywords
cobalt 60, DNA, pentoxifylline, protein p53, animal cell, apoptosis, article, cell death, cell strain 3T3, controlled study, DNA repair, flow cytometry, gamma irradiation, gene mutation, mouse, nonhuman, priority journal, radiosensitization, 3T3 Cells, Animals, Apoptosis, Cell Survival, DNA, DNA Repair, Dose-Response Relationship, Radiation, Fibroblasts, G2 Phase, Gamma Rays, Mice, Mutagenesis, Site-Directed, Pentoxifylline, Radiation Tolerance, Radiation-Protective Agents, Transfection, Tumor Suppressor Protein p53, Animalia, Murinae
Citation
International Journal of Radiation Biology
78
11
78
11