title: Low doses of gamma-irradiation induce an early bystander effect in zebrafish cells which is sufficient to radioprotect cells.
abstract: The term "bystander effect" is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01-0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of γ-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less γ-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less γ-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, PRP-Environnement/SERIS, Laboratoire d'Ecotoxicologie des Radionucléides, Cadarache, St Paul Lez Durance, France; CRCL - UMR INSERM 1052 - CNRS 5286, Equipe de Radiobiologie, Cheney A- 1éme étage, Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pereira
authors.affiliation: CEA, DSV, IBEB, Lab Biochim System Perturb, Bagnols-sur-Cèze, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Malard
authors.affiliation: Laboratoire des Lésions des Acides Nucléiques, INAC/Scib UMR E3 CEA-UJF, CEA Grenoble, Grenoble, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
authors.affiliation: CEA, DSV, IBEB, Lab Biochim System Perturb, Bagnols-sur-Cèze, France.
authors.forename: Anne-Hélène
authors.initials: AH
authors.lastname: Davin
authors.affiliation: CEA, DSV, IBEB, Lab Biochim System Perturb, Bagnols-sur-Cèze, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Armengaud
authors.affiliation: CRCL - UMR INSERM 1052 - CNRS 5286, Equipe de Radiobiologie, Cheney A- 1éme étage, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foray
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, PRP-Environnement/SERIS, Laboratoire d'Ecotoxicologie des Radionucléides, Cadarache, St Paul Lez Durance, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Adam-Guillermin
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects*; D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D019175:DNA Methylation / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D044127:Epigenesis, Genetic / Q000528:radiation effects; D005720:Gamma Rays; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D011835:Radiation Protection; D013997:Time Factors; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D006657:Histones; D029961:Zebrafish Proteins