Journal article
Base excision repair of both uracil and oxidatively damaged bases contribute to thymidine deprivation-induced radiosensitization
International journal of radiation oncology, biology, physics, Vol.65(5), pp.1544-1552
2006
DOI: 10.1016/j.ijrobp.2006.03.051
PMID: 16863931
Abstract
Purpose: Increased cellular sensitivity to ionizing radiation due to thymidine depletion is the basis of radiosensitization with fluoropyrimidine and methotrexate. The mechanism responsible for cytotoxicity has not been fully elucidated but appears to involve both the introduction of uracil into, and its removal from, DNA. The role of base excision repair of uracil and oxidatively damaged bases in creating the increased radiosensitization during thymidine depletion is examined.
Methods and Materials: Isogenic strains of
S. cerevisiae differing only at loci involved in DNA repair functions were exposed to aminopterin and sulfanilamide to induce thymidine deprivation. Cultures were irradiated and survival determined by clonogenic survival assay.
Results: Strains lacking uracil base excision repair (BER) activities demonstrated less radiosensitization than the parental strain. Mutant strains continued to show partial radiosensitization with aminopterin treatment. Mutants deficient in BER of both uracil and oxidatively damaged bases did not demonstrate radiosensitization. A recombination deficient
rad52 mutant strain was markedly sensitive to radiation; addition of aminopterin increased radiosensitivity only slightly. Radiosensitization observed in
rad52 mutants was also abolished by deletion of the
APN1,
NTG1, and
NTG2 genes.
Conclusion: These data suggest radiosensitization during thymidine depletion is the result of BER activities directed at both uracil and oxidatively damaged bases.
Details
- Title: Subtitle
- Base excision repair of both uracil and oxidatively damaged bases contribute to thymidine deprivation-induced radiosensitization
- Creators
- Bryan G Allen - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, USAMonika Johnson - Department of Radiation Oncology, University of Iowa Health Care, Iowa City, IA, USAAnne E Marsh - Department of Radiation Oncology, University of Iowa Health Care, Iowa City, IA, USAKenneth J Dornfeld - Department of Radiation Oncology, University of Iowa Health Care, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- International journal of radiation oncology, biology, physics, Vol.65(5), pp.1544-1552
- DOI
- 10.1016/j.ijrobp.2006.03.051
- PMID
- 16863931
- NLM abbreviation
- Int J Radiat Oncol Biol Phys
- ISSN
- 0360-3016
- eISSN
- 1879-355X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2006
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984046902602771
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