Autophagy as an Ultrastructural Marker of Heavy Metal Toxicity in Human Cord Blood Hematopoietic Stem Cells

Stem cells are increasingly recognised as a target of environmental toxicants in carcinogenesis, 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 hours 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 indicative for 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, and at ultrastructural level cells showed only 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. Because autophagy may contribute to carcinogenesis and chronic diseases, autophagic alterations, assessed by in vitro assays based on hematopoietic stem cells, could be markers of toxic exposure to heavy metals.

DI GIOACCHINO M.;  PETRARCA C.;  PERRONE A.;  FARINA Massimo;  SABBIONI Enrico;  HARTUNG Thomas;  MARTINO Simone;  ESPOSITO Diana L.;  LOTTI Lavinia Vittoria;  MARIANI-COSTANTINI Renato; 

2008-12-03

ELSEVIER SCIENCE BV

JRC38145

0048-9697,   

http://dx.doi.org/10.1016/j.scitotenv.2007.11.009,    https://publications.jrc.ec.europa.eu/repository/handle/JRC38145,   

10.1016/j.scitotenv.2007.11.009,