Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells

Mario Di Gioacchino, Claudia Petrarca, Angela Perrone, Massimo Farina, Enrico Sabbioni, Thomas Hartung, Simone Martino, Diana L. Esposito, Lavinia Vittoria Lotti, Renato Mariani-Costantini

Research output: Contribution to journalArticle

Abstract

Stem cells are a key target of environmental toxicants, but little is known about their toxicological responses. We aimed at developing an in-vitro model based on adult human stem cells to identify biomarkers of heavy metal exposure. To this end we investigated the responses of human CD34+ hematopoietic progenitor cells to hexavalent chromium (Cr[VI]) and cadmium (Cd). Parallel cultures of CD34+ cells isolated from umbilical cord blood were exposed for 48 h to 0.1 μM and 10 μM Cr(VI) or Cd. Cultures treated with 10 μM Cr(VI) or Cd showed marked cell loss. Ultrastructural analysis of surviving cells revealed prominent autophagosomes/autophagolysosomes, which is diagnostic of autophagy, associated with mitochondrial damage and replication, dilatation of the rough endoplasmic reticulum and Golgi complex, cytoplasmic lipid droplets and chromatin condensation. Treated cells did not show the morphologic hallmarks of apoptosis. Treatment with 0.1 μM Cr(VI) or Cd did not result in cell loss, but at the ultrastructural level cells showed dilated endoplasmic reticulum and evidence of mitochondrial damage. We conclude that autophagy is implicated in the response of human hematopoietic stem cells to toxic concentrations of Cr(VI) and Cd. Autophagy, which mediates cell survival and death under stress, deserves further evaluation to be established as biomarker of metal exposure.

Original languageEnglish (US)
Pages (from-to)50-58
Number of pages9
JournalScience of the Total Environment
Volume392
Issue number1
DOIs
StatePublished - Mar 15 2008
Externally publishedYes

Keywords

  • Autophagy
  • CD34+ cells
  • Cadmium
  • Chromium
  • In-vitro assay
  • Stem cells
  • Toxicity
  • Umbilical cord blood

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

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  • Cite this

    Di Gioacchino, M., Petrarca, C., Perrone, A., Farina, M., Sabbioni, E., Hartung, T., Martino, S., Esposito, D. L., Lotti, L. V., & Mariani-Costantini, R. (2008). Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells. Science of the Total Environment, 392(1), 50-58. https://doi.org/10.1016/j.scitotenv.2007.11.009