Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation

// Sandrine Roch-Lefevre 1 , Eric Gregoire 1 , Cecile Martin-Bodiot 1 , Matthew Flegal 2 , Amelie Freneau 1 , Melinda Blimkie 2 , Laura Bannister 2 , Heather Wyatt 2 , Joan-Francesc Barquinero 5 , Laurence Roy 1 , Mohamed Benadjaoud 1 , Nick Priest 2 , Jean-Rene Jourdain 3 and Dmitry Klokov 2, 4 1 Institut de Radioprotection et de Surete Nucleaire, IRSN, Pole Sante et Environnement, Direction de la Sante, Fontenay-aux-Roses, France 2 Radiobiology and Health, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada 3 Institut de Radioprotection et de Surete Nucleaire, IRSN, Direction des Affaires Internationales, Fontenay-aux-Roses, France 4 Department of Biochemistrty, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada 5 Present address at: Autonomous University of Barcelona, Faculty of Biosciences, Cerdanyola del Valles, Spain Correspondence to: Sandrine Roch-Lefevre, email: sandrine.roch-lefevre@irsn.fr Dmitry Klokov, email: dmitry.klokov@cnl.ca Keywords: genotoxicity; chronicle; low-dose; tritium exposure Received: July 29, 2017      Accepted: March 23, 2018      Published: June 08, 2018 ABSTRACT The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 – 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo , the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.