title: Tritium contamination of hematopoietic stem cells alters long-term hematopoietic reconstitution.
abstract: OBJECTIVE
  In vivo effects of tritium contamination are poorly documented. Here, we study the effects of tritiated Thymidine ([(3)H] Thymidine) or tritiated water (HTO) contamination on the biological properties of hematopoietic stem cells (HSC).
  
  
  METHODS
  Mouse HSC were contaminated with concentrations of [(3)H] Thymidine ranging from 0.37-37.03 kBq/ml or of HTO ranging from 5-50 kBq/ml. The biological properties of contaminated HSC were studied in vitro after HTO contamination and in vitro and in vivo after [(3)H] Thymidine contamination.
  
  
  RESULTS
  Proliferation, viability and double-strand breaks were dependent on [(3)H] Thymidine or HTO concentrations used for contamination but in vitro myeloid differentiation of HSC was not affected by [(3)H] Thymidine contamination. [(3)H] Thymidine contaminated HSC showed a compromised long-term capacity of hematopoietic reconstitution and competition experiments showed an up to two-fold decreased capacity of contaminated HSC to reconstitute hematopoiesis. These defects were not due to impaired homing in bone marrow but to an initial decreased proliferation rate of HSC.
  
  
  CONCLUSIONS
  These results indicate that contaminations of HSC with doses of tritium that do not result in cell death, induce short-term effects on proliferation and cell cycle and long-term effects on hematopoietic reconstitution capacity of contaminated HSC.
authors.affiliation: Commissariat à l'Energie Atomique (CEA)/Direction des Sciences du Vivant (DSV)/Institut de Radiobiologie Cellulaire et Moléculaire (iRCM)/Laboratoire de recherche sur la Réparation et la Transcription dans les cellules Souches (LRTS, Fontenay-aux-Roses cedex, 92265.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Giacomo
authors.forename: Christine
authors.initials: C
authors.lastname: Granotier
authors.forename: Vilma
authors.initials: V
authors.lastname: Barroca
authors.forename: David
authors.initials: D
authors.lastname: Laurent
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewandowski
authors.forename: Yannick
authors.initials: Y
authors.lastname: Saintigny
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Romeo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001345:Autoradiography / Q000379:methods; D001853:Bone Marrow / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002453:Cell Cycle; D049109:Cell Proliferation; D005434:Flow Cytometry / Q000379:methods; D006410:Hematopoiesis / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells; D014316:Tritium / Q000494:pharmacology*
chemical_list: C468783:H2AX protein, human; D006657:Histones; D014316:Tritium