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Title: Prolonged expression of the γ-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment.
Authors: Bourton, EC
Plowman, PN
Smith, D
Arlett, CF
Parris, CN
Keywords: Normal tissue toxicity
Predictive testing
DNA repair
Publication Date: 2011
Publisher: UICC
Citation: International Journal of Cancer (Early Online), Feb 2011
Abstract: The normal tissue tolerance levels to fractionated radiotherapy have been appreciated by a century of careful clinical observations and radiobiological studies in animals. During clinical fractionated radiotherapy, these normal tissue tolerance levels are respected, and severe sequelae of radiotherapy are avoided in the majority of patients. Notwithstanding, a minority of patients experience unexpectedly severe normal tissue reactions. The ability to predict which patients might form this minority would be important. We have conducted a study to develop a rapid and reliable diagnostic test to predict excessive normal tissue toxicity (NTT) in radiotherapy patients. A flow cytometric immunocytochemical assay was used to measure DNA damage in peripheral blood lymphocytes (PBL) from cancer patients exposed to 2-Gy gamma radiation. DNA damage and repair was measured by induction of cellular γ-H2AX in unirradiated and exposed cells at specific time points following exposure. In 12 cancer patients that experienced severe atypical NTT following radiotherapy, there was a failure to repair DNA double-strand breaks (DSB) as measured by γ-H2AX induction and persistence. In ten cancer patients that experienced little or no NTT and in seven normal (noncancer controls), efficient repair of DNA DSB was observed in the γ-H2AX assay. We conclude that a flow cytometric assay based on γ-H2AX induction in PBL of radiotherapy patients may represent a robust, rapid and reliable biomarker to predict NTT during radiotherapy. Further research is required with a larger patient cohort to validate this important study.
Description: This work was funded by the National Institutes of Health Research (New and Emerging Applications of Technology Initiative), and Barts and the London Charity. This article is available from the specified link - Copyright @ 2011 UICC
Sponsorship: This article has been made available through the Brunel Open Access Publishing Fund.
ISSN: 1097-0215
Appears in Collections:School of Engineering and Design Research papers
Electronic and Computer Engineering
Biological Sciences
Community Health and Public Health
Brunel OA Publishing Fund
Dept of Life Sciences Research Papers

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