Document Detail


Azidothymidine enhances fluorodeoxyuridine-mediated radiosensitization.
MedLine Citation:
PMID:  20159365     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To examine the role of DNA repair and altered thymidine analogues in altering the response to radiation during thymidine deprivation.
METHODS AND MATERIALS: Mismatch repair-deficient and -proficient cell lines HEC59 and HC-2.4 were treated with fluorodeoxyuridine (FUdR), azidothymidine (AZT), and irradiation either alone or in combination, and outcomes of clonogenic survival and cell-cycle distributions were determined.
RESULTS: Survival outcomes for all treatments were similar for both cell lines, suggesting that hMSH2 does not significantly influence thymidine deprivation toxicity or radiosensitization. The chain-terminating thymidine analogue AZT increased the toxicity of FUdR and increased DNA fragmentation. The combination of FUdR and AZT afforded greater radiosensitization than either drug alone. Drug enhancement ratios, the degree of excess radiation-induced cell death in drug-treated cultures compared with radiation alone for HEC59, were 1.2, 1.4, and 1.8 for AZT, FUdR, and the combination, respectively. Enhancement ratios for HC-2.4 were 1.3, 1.5, and 1.8 for AZT, FUdR, and the combination, respectively.
CONCLUSION: Azidothymidine, a chain-terminating thymidine analogue, can enhance the radiosensitizing affects of thymidine deprivation. Deoxyribonucleic acid strand breaks may play an important role in the mechanism of thymidine deprivation-induced radiosensitization.
Authors:
Chang-Ming Chen; Monika Johnson; Brian J Smith; Ken Dornfeld
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  76     ISSN:  1879-355X     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-03-05     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  905-13     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 55805, USA.
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MeSH Terms
Descriptor/Qualifier:
Antimetabolites / metabolism,  pharmacology*
Cell Cycle / drug effects,  physiology
Cell Line, Tumor
Cell Survival / drug effects,  genetics,  radiation effects
Colony-Forming Units Assay / methods
DNA Breaks, Single-Stranded*
DNA Damage
DNA Mismatch Repair / physiology
Deoxyuracil Nucleotides / metabolism
Drug Synergism
Flow Cytometry
Floxuridine / metabolism,  pharmacology*
Humans
MutS Homolog 2 Protein / metabolism
Poisson Distribution
Radiation Tolerance / drug effects*,  genetics
Thymidine / metabolism*
Thymine Nucleotides / metabolism
Zidovudine / metabolism,  pharmacology*
Grant Support
ID/Acronym/Agency:
7K08CA111404-02/CA/NCI NIH HHS; K08 CA111404-01A1/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antimetabolites; 0/Deoxyuracil Nucleotides; 0/Thymine Nucleotides; 1173-82-6/deoxyuridine triphosphate; 30516-87-1/Zidovudine; 365-08-2/thymidine 5'-triphosphate; 50-89-5/Thymidine; 50-91-9/Floxuridine; EC 3.6.1.3/MSH2 protein, human; EC 3.6.1.3/MutS Homolog 2 Protein
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