Impact of dose-rate on the low-dose hyper-radiosensitivity and induced radioresistance (HRS/IRR) response* October 2013, Vol. 89, No. 10 , Pages 813-822 (doi:10.3109/09553002.2013.800248) Charles Thomas 1, Jennifer Martin 1, Clément Devic 1, Elke Bräuer-Krisch 2, Michel Diserbo 3, Juliette Thariat 4 & Nicolas Foray 1 1Institut National de la Santé et de la Recherche Médicale (INSERM) U 1052, groupe de radiobiologie, Lyon 2European Synchrotron Radiation Facility, Grenoble 3Institut de Recherche Biomédicale des Armées (IRBA), BP 87, 38702 La Tronche 4Centre Antoine Lacassagne, Radiotherapy unit, Nice, France *The authors dedicate this work to Bernard Fertil for his contribution to radiobiology. Correspondence: Charles Thomas, Inserm U1052, Centre de Recherche en Cancérologie de Lyon, 28 Rue Laënnec, 69008 Lyon, France. Tel: + 33 6 9826 1603, E-mail: [email protected] Abstract Purpose: To ask whether dose-rate influences low-dose hyper- radiosensitivity and induced radioresistance (HRS/IRR) response in rat colon progressive (PRO) and regressive (REG) cells. Methods: Clonogenic survival was applied to tumorigenic PRO and non-tumorigenic REG cells irradiated with 60Co γ-rays at 0.0025–500 mGy.min−1. Both clonogenic survival and non-homologous end-joining (NHEJ) pathway involved in DNA double-strand breaks (DSB) repair assays were applied to PRO cells irradiated at 25 mGy.min−1 with 75 kV X-rays only. Results: Irrespective of dose-rates, marked HRS/IRR responses were observed in PRO but not in REG cells. For PRO cells, the doses at which HRS and IRR responses are maximal were dependent on dose-rate; conversely exposure times during which HRS and IRR responses are maximal (tHRSmax and tIRRmax) were independent of dose-rate. The tHRSmax and tIRRmax values were 23 ± 5 s and 66 ± 7 s (mean ± standard error of the mean [SEM], n = 7), in agreement with literature data. Repair data show that tHRSmax may correspond to exposure time during which NHEJ is deficient while tIRRmax may correspond to exposure time during which NHEJ is complete. Conclusion: HRS response may be maximal if exposure times are shorter than tHRSmax irrespective of dose, dose-rate and cellular model. Potential application of HRS response in radiotherapy is discussed.
Posted on: Wed, 02 Oct 2013 12:51:04 +0000
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