Tritium contamination of hematopoietic stem cells alters long-term hematopoietic reconstitution

Abstract

Purpose: In vivo effects of tritium contamination are poorly documented. Here, we study the effects of tritiated Thymidine ([3H] Thymidine) or tritiated water (HTO) contamination on the biological properties of hematopoietic stem cells (HSC).Materials and methods: Mouse HSC were contaminated with concentrations of [3H] 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 [3H] Thymidine contamination.Results: Proliferation, viability and double-strand breaks were dependent on [3H] Thymidine or HTO concentrations used for contamination but in vitro myeloid differentiation of HSC was not affected by [3H] Thymidine contamination. [3H] 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.Conclusion: 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.