Document Detail

Radiosensitization and DNA repair inhibition by pentoxifylline in NIH3T3 p53 transfectants.
MedLine Citation:
PMID:  12456286     Owner:  NLM     Status:  MEDLINE    
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 Co(60) gamma-irradiation by colony assay. DNA repair (0-100 Gy) 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 SF(10) radiotoxicity enhancement factors induced by the pentoxifylline were 8.0 and 9.7, respectively. In the p53 deletion mutant p53-DeltaA 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.
A Binder; T Theron; H Donninger; M Parker; L Bohm
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  78     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-28     Completed Date:  2002-12-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  991-1000     Citation Subset:  IM; S    
Department of Radiation Oncology, Radiobiology Laboratory, University of Stellenbosch, Faculty of Health and Tygerberg Hospital, PO Box 19063, Tygerberg 7505, South Africa.
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MeSH Terms
3T3 Cells
Apoptosis / drug effects,  radiation effects
Cell Survival / drug effects,  radiation effects
DNA / chemistry,  radiation effects
DNA Repair / drug effects*
Dose-Response Relationship, Radiation
Fibroblasts / cytology,  drug effects*,  metabolism,  radiation effects
G2 Phase / radiation effects
Gamma Rays
Mutagenesis, Site-Directed
Pentoxifylline / pharmacology*
Radiation Tolerance / drug effects*
Radiation-Protective Agents / pharmacology*
Tumor Suppressor Protein p53 / biosynthesis*,  genetics
Reg. No./Substance:
0/Radiation-Protective Agents; 0/Tumor Suppressor Protein p53; 6493-05-6/Pentoxifylline; 9007-49-2/DNA

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