Inorganic arsenic induces necrosis of human CD34-positive haematopoietic stem cells

Authors

  • Laurent Vernhet,

    Corresponding author
    1. INSERM U620, Détoxication et Réparation Tissulaire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France
    • INSERM U620, Détoxication et Réparation Tissulaire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France
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  • Claudie Morzadec,

    1. INSERM U620, Détoxication et Réparation Tissulaire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France
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  • Julien van Grevenynghe,

    1. INSERM U620, Détoxication et Réparation Tissulaire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France
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  • Benoît Bareau,

    1. Département HITC, Centre Hospitalier Universitaire Rennes, 2 rue Henri Le Guilloux, 35033 Rennes, France
    2. Service d'Hématologie Clinique, Centre Hospitalier Universitaire Rennes, 2 rue Henri Le Guilloux, 35033 Rennes, France
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  • Michel Corolleur,

    1. Département HITC, Centre Hospitalier Universitaire Rennes, 2 rue Henri Le Guilloux, 35033 Rennes, France
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  • Thierry Fest,

    1. Département HITC, Centre Hospitalier Universitaire Rennes, 2 rue Henri Le Guilloux, 35033 Rennes, France
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  • Olivier Fardel

    1. INSERM U620, Détoxication et Réparation Tissulaire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France
    2. Département HITC, Centre Hospitalier Universitaire Rennes, 2 rue Henri Le Guilloux, 35033 Rennes, France
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Abstract

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 μM) 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. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.

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