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

Fingerprint

Heavy Metals
Stem cells
Cadmium
Heavy metals
Toxicity
Blood
cadmium
blood
stem
heavy metal
toxicity
Biomarkers
biomarker
Cells
damage
apoptosis
Cell death
Poisons
Lipids
droplet

Keywords

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

ASJC Scopus subject areas

  • Environmental Chemistry
  • Environmental Science(all)

Cite this

Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells. / Di Gioacchino, Mario; Petrarca, Claudia; Perrone, Angela; Farina, Massimo; Sabbioni, Enrico; Hartung, Thomas; Martino, Simone; Esposito, Diana L.; Lotti, Lavinia Vittoria; Mariani-Costantini, Renato.

In: Science of the Total Environment, Vol. 392, No. 1, 15.03.2008, p. 50-58.

Research output: Contribution to journalArticle

Di Gioacchino, M, Petrarca, C, Perrone, A, Farina, M, Sabbioni, E, Hartung, T, Martino, S, Esposito, DL, Lotti, LV & 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, vol. 392, no. 1, pp. 50-58. https://doi.org/10.1016/j.scitotenv.2007.11.009
Di Gioacchino, Mario ; Petrarca, Claudia ; Perrone, Angela ; Farina, Massimo ; Sabbioni, Enrico ; Hartung, Thomas ; Martino, Simone ; Esposito, Diana L. ; Lotti, Lavinia Vittoria ; Mariani-Costantini, Renato. / Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells. In: Science of the Total Environment. 2008 ; Vol. 392, No. 1. pp. 50-58.
@article{1fe7056a541a4a46bd7980914cf4b319,
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 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.",
keywords = "Autophagy, Cadmium, CD34+ cells, Chromium, In-vitro assay, Stem cells, Toxicity, Umbilical cord blood",
author = "{Di Gioacchino}, Mario and Claudia Petrarca and Angela Perrone and Massimo Farina and Enrico Sabbioni and Thomas Hartung and Simone Martino and Esposito, {Diana L.} and Lotti, {Lavinia Vittoria} and Renato Mariani-Costantini",
year = "2008",
month = "3",
day = "15",
doi = "10.1016/j.scitotenv.2007.11.009",
language = "English (US)",
volume = "392",
pages = "50--58",
journal = "Science of the Total Environment",
issn = "0048-9697",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells

AU - Di Gioacchino, Mario

AU - Petrarca, Claudia

AU - Perrone, Angela

AU - Farina, Massimo

AU - Sabbioni, Enrico

AU - Hartung, Thomas

AU - Martino, Simone

AU - Esposito, Diana L.

AU - Lotti, Lavinia Vittoria

AU - Mariani-Costantini, Renato

PY - 2008/3/15

Y1 - 2008/3/15

N2 - 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.

AB - 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.

KW - Autophagy

KW - Cadmium

KW - CD34+ cells

KW - Chromium

KW - In-vitro assay

KW - Stem cells

KW - Toxicity

KW - Umbilical cord blood

UR - http://www.scopus.com/inward/record.url?scp=38549101930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38549101930&partnerID=8YFLogxK

U2 - 10.1016/j.scitotenv.2007.11.009

DO - 10.1016/j.scitotenv.2007.11.009

M3 - Article

C2 - 18166216

AN - SCOPUS:38549101930

VL - 392

SP - 50

EP - 58

JO - Science of the Total Environment

JF - Science of the Total Environment

SN - 0048-9697

IS - 1

ER -