Journal article
Azidothymidine Enhances Fluorodeoxyuridine-Mediated Radiosensitization
International journal of radiation oncology, biology, physics, Vol.76(3), pp.905-913
2010
DOI: 10.1016/j.ijrobp.2009.09.016
PMCID: PMC2900777
PMID: 20159365
Abstract
To examine the role of DNA repair and altered thymidine analogues in altering the response to radiation during thymidine deprivation.
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.
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.
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.
Details
- Title: Subtitle
- Azidothymidine Enhances Fluorodeoxyuridine-Mediated Radiosensitization
- Creators
- Chang-Ming Chen - Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IAMonika Johnson - Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IABrian J Smith - College of Public Health, University of Iowa, Iowa City, IAKen Dornfeld - Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- International journal of radiation oncology, biology, physics, Vol.76(3), pp.905-913
- DOI
- 10.1016/j.ijrobp.2009.09.016
- PMID
- 20159365
- PMCID
- PMC2900777
- NLM abbreviation
- Int J Radiat Oncol Biol Phys
- ISSN
- 0360-3016
- eISSN
- 1879-355X
- Publisher
- Elsevier Inc
- Grant note
- 7K08CA111404-02 / National Cancer Institute
- Language
- English
- Date published
- 2010
- Academic Unit
- Biostatistics; Holden Comprehensive Cancer Center
- Record Identifier
- 9983997358802771
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