title: Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells.
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 microM and 10 microM Cr(VI) or Cd. Cultures treated with 10 microM 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 microM 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.
authors.affiliation: Aging Research Center, G. d'Annunzio University Foundation, Via Colle dell'Ara, Chieti, Italy. m.digioacchino@unich.it
authors.forename: Mario
authors.initials: M
authors.lastname: Di Gioacchino
authors.forename: Claudia
authors.initials: C
authors.lastname: Petrarca
authors.forename: Angela
authors.initials: A
authors.lastname: Perrone
authors.forename: Massimo
authors.initials: M
authors.lastname: Farina
authors.forename: Enrico
authors.initials: E
authors.lastname: Sabbioni
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Simone
authors.initials: S
authors.lastname: Martino
authors.forename: Diana L
authors.initials: DL
authors.lastname: Esposito
authors.forename: Lavinia Vittoria
authors.initials: LV
authors.lastname: Lotti
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology; D001343:Autophagy; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D006801:Humans; D019216:Metals, Heavy / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission
chemical_list: D018952:Antigens, CD34; D019216:Metals, Heavy