title: Homologous recombination is involved in the repair response of mammalian cells to low doses of tritium.
abstract: Radioactive compounds incorporated in tissues can have biological effects resulting from energy deposition in subcellular compartments. We addressed the genetic consequences of [(3)H] or [(14)C]thymidine incorporation into mammalian DNA. Low doses of [(3)H]thymidine in CHO cells led to enhanced sensitivity compared with [(14)C]thymidine. Compared with wild-type cells, homologous recombination (HR)-deficient cells were more sensitive to lower doses of [(3)H]thymidine but not to any dose of [(14)C]thymidine. XRCC4-defective cells, however, were sensitive to both low and high doses of [(3)H] and [(14)C]thymidine, suggesting introduction of DNA double-strand breaks, which were confirmed by gamma-H2AX focus formation. While gamma rays induced measurable HR only at toxic doses, sublethal levels of [(3)H] or [(14)C]thymidine strongly induced HR. The level of stimulation was in an inverse relationship to the emitted energies. The RAD51 gene conversion pathway was involved, because [(3)H]thymidine induced RAD51 foci, and [(3)H]thymidine-induced HR was abrogated by expression of dominant negative RAD51. In conclusion, both HR and non-homologous end-joining pathways were involved after labeled nucleotide incorporation (low doses); genetic effects were negatively correlated with the energy emitted but were positively correlated with the energy deposited in the nucleus, suggesting that low-energy beta-particle emitters, at non-toxic doses, may induce genomic instability.
authors.affiliation: Institut de Radiobiologie Cellulaire et Moleculaire, CEA-Centre National de la Recherche Scientifique, UMR 217, Fontenay-aux-Roses Cédex, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Saintigny
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roche
authors.forename: Delphine
authors.initials: D
authors.lastname: Meynard
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Lopez
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D011829:Radiation Dosage; D011995:Recombination, Genetic / Q000235:genetics* / Q000528:radiation effects*; D014316:Tritium / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D014316:Tritium