Title: MRE11 and H2AX biomarkers in the response to low-dose exposure: balance between individual susceptibility to radiosensitivity and to genomic instability

Authors: C. Colin; A. Granzotto; C. Devic; C. Massart; M. Viau; G. Vogin; M. Maalouf; A. Joubert; N. Foray

Addresses: Service de Radiologie, Centre Hospitalo Universitaire Lyon-Sud, 69490, Pierre Bénite, France; EA3738, Faculté de Médecine Lyon-Sud, 69921 Oullins, France. ' INSERM, CR-U1052, Radiobiology Group, Cancer Research Centre, 28 Rue Laennec, 69008 Lyon, France. ' INSERM, CR-U1052, Radiobiology Group, Cancer Research Centre, 28 Rue Laennec, 69008 Lyon, France. ' INSERM, CR-U1052, Radiobiology Group, Cancer Research Centre, 28 Rue Laennec, 69008 Lyon, France. ' INSERM, CR-U1052, Radiobiology Group, Cancer Research Centre, 28 Rue Laennec, 69008 Lyon, France. ' INSERM, CR-U1052, Radiobiology Group, Cancer Research Centre, 28 Rue Laennec, 69008 Lyon, France. ' INSERM, CR-U1052, Radiobiology Group, Cancer Research Centre, 28 Rue Laennec, 69008 Lyon, France; Centre National d’Etudes Spatiales, Place Maurice Quentin, 75001 Paris, France. ' Société Magelis, 84160 Cadenet, France. ' INSERM, CR-U1052, Radiobiology Group, Cancer Research Centre, 28 Rue Laennec, 69008 Lyon, France

Abstract: Unrepaired and misrepaired DNA Double-Strand Breaks (DSBs) were shown to be the key events of radiation-induced toxicity (radiosensitivity) and genomic instability (cancer proneness), respectively. We have previously shown that immunofluorescence with ?-H2AX and MRE11 biomarkers may account for unrepaired and misrepaired DSBs for doses higher than 1 Gy. Three radiosensitivity groups had been defined (group I: radioresistance; group II: moderate radiosensitivity and cancer proneness; group III: hyper-radiosensitivity). Here, we investigated X-ray doses ranging from 9 mGy to 2 Gy in three cell lines representative of these radiosensitivity groups. We observed a non-linear dose-dependent increase of the severity of DSB, suggesting a correlation with the phenomenon of hyper-radiosensitivity to low dose; a non-linear dose-dependent increase of MRE11 foci, revealing a dose-threshold for the radiation-induced genomic instability. Altogether, these data document the evidence of a threshold in low-dose response and strongly suggest the impact of individual factor.

Keywords: DSB repair; gamma-H2AX; MRE11; biomarkers; low-dose irradiation; low radiation; individual susceptibility; radiosensitivity; genomic instability; DNA double-strand breaks; X-ray doses; immunofluorescence.

DOI: 10.1504/IJLR.2011.044191

International Journal of Low Radiation, 2011 Vol.8 No.2, pp.96 - 106

Published online: 07 Feb 2015 *

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