Min Liu1,2, Solah Lee2, Bailong Liu1,2, Hongyan Wang2, Lihua Dong1, Ya Wang2. 1. Department of Radiation Oncology, the First Hospital, Jilin University, Changchun, 130021, China. 2. Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Abstract
PURPOSE: Sublethal damage repair (SLDR) is a type of repair that occurs in split-dose irradiated cells, which was discovered more than 50 years ago. However, due to conflicting reported data, it remains unclear which DNA double-strand break (DSB) repair pathway, non-homologous end-joining (NHEJ) repair, homologous recombination repair (HRR) or both, contributes to SLDR, particularly in human cells. We were interested in clarifying this question. METHODS AND MATERIALS: Mammalian cell lines, including human, mouse and Chinese hamster ovary (CHO) cell lines, wild type, deficient in NHEJ or HRR were irradiated with either single dose or two split doses at 2- or 4-h intervals. The clonogenic assay was used to evaluate these cell radiosensitivities. RESULTS: All wild-type or HRR-deficient cells (including human, mouse and CHO cells) showed a higher survival rate after exposure to split-dose versus single-dose radiation; however, all classical NHEJ-deficient cells (including human, mouse and hamster cells) did not show any apparent sensitivity changes between single-dose and split-dose irradiation. CONCLUSION: Classical NHEJ mainly contributes to SLDR in mammalian cells (including human cells). These results have the potential to improve radiotherapy.
PURPOSE: Sublethal damage repair (SLDR) is a type of repair that occurs in split-dose irradiated cells, which was discovered more than 50 years ago. However, due to conflicting reported data, it remains unclear which DNA double-strand break (DSB) repair pathway, non-homologous end-joining (NHEJ) repair, homologous recombination repair (HRR) or both, contributes to SLDR, particularly in human cells. We were interested in clarifying this question. METHODS AND MATERIALS: Mammalian cell lines, including human, mouse and Chinese hamster ovary (CHO) cell lines, wild type, deficient in NHEJ or HRR were irradiated with either single dose or two split doses at 2- or 4-h intervals. The clonogenic assay was used to evaluate these cell radiosensitivities. RESULTS: All wild-type or HRR-deficient cells (including human, mouse and CHO cells) showed a higher survival rate after exposure to split-dose versus single-dose radiation; however, all classical NHEJ-deficient cells (including human, mouse and hamster cells) did not show any apparent sensitivity changes between single-dose and split-dose irradiation. CONCLUSION: Classical NHEJ mainly contributes to SLDR in mammalian cells (including human cells). These results have the potential to improve radiotherapy.
Entities:
Keywords:
DNA DSB; DNA repair; HRR; NHEJ; SLDR; heavy ion
Authors: Carsten Herskind; Lin Ma; Qi Liu; Bo Zhang; Frank Schneider; Marlon R Veldwijk; Frederik Wenz Journal: Radiat Oncol Date: 2017-01-19 Impact factor: 3.481
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