期刊
RADIOTHERAPY AND ONCOLOGY
卷 101, 期 1, 页码 28-34出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2011.09.021
关键词
Individual radiosensitivity; Cancer predisposition; G2-assay; G2-checkpoint; Caffeine; Chromatid breaks; DNA damage repair; Ataxia Telangiectasia (AT)
Background and purpose: An increased yield of chromatid breaks following G2-phase irradiation could be a marker of radiosensitivity-predisposing genes that respond to DNA damage. We have shown that the dynamic nature of chromatin-nucleoprotein complex, which is capable of rapid unfolding, disassembling, assembling and refolding, affects repair of radiation-induced DNA-lesions and causes chromatid breaks during G2-M transition in damaged DNA sites. Here, we investigate induction and repair kinetics of chromatid breaks, their potential role in radiosensitivity predisposition and a standardized G2-assay is proposed to assess individual radiosensitivity. Materials and methods: Lymphocytes from 125 blood donors with significant inter-individual radiosensitivity variation (healthy, cancer, AT-patients) are used to correlate G2-checkpoint efficiency with chromatid breakage and individual radiosensitivity. Experiments involve repair kinetics of chromatid breaks using colcemid-block and treatment with caffeine to abrogate G2-checkpoint, generate internal controls and standardize the G2-assay. Results: Radiation-induced chromatid breaks during G2-M transition, following 4 h repair, remained unchanged and a significant correlation between G2-chromosomal radiosensitivity and G2-checkpoint efficiency to prevent chromatid breakage was found. A standardized G2-assay is developed by introducing normalization to conditions reflecting lack of checkpoint and repair similar to those of AT-patients, generating a unique standard for individual radiosensitivity testing. Conclusions: The standardized G2-assay can minimize inter-laboratory and intra-experimental variations and may have straightforward application in clinical practice for individualization of radiotherapy protocols. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 28-34
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