Inorganic arsenic induces necrosis of human CD34-positive haematopoietic stem cells.
Inorganic arsenic is a major environmental contaminant known to exert immunosuppressive effects. In this study, we report toxicity of As2O3, a trivalent inorganic form, toward isolated human hematopoietic CD34+ progenitor cells. Our results demonstrate that low concentrations of As2O3 (0.1-5 microM) inhibit in vitro proliferation of CD34+ cells and their differentiation into various hematological cell lineages. These effects were associated with the induction of a necrotic process independent of caspases and likely related to mitochondrial damage. We conclude that As2O3 can impair in vitro human hematopoiesis by decreasing survival of CD34+ progenitor cells.
Vernhet
Laurent
L
INSERM U620, Détoxication et Réparation Tissulaire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France. Laurent.Vernhet@rennes.inserm.fr
Morzadec
Claudie
C
van Grevenynghe
Julien
J
Bareau
Benoît
B
Corolleur
Michel
M
Fest
Thierry
T
Fardel
Olivier
O
D018952:Antigens, CD34 / Q000378:metabolism*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis; D010087:Oxides / Q000633:toxicity*
D018952:Antigens, CD34; D001152:Arsenicals; D004785:Environmental Pollutants; D010087:Oxides; D000077237:Arsenic Trioxide