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 language | English (US) |
|---|---|
| Pages (from-to) | 50-58 |
| Number of pages | 9 |
| Journal | Science of the Total Environment |
| Volume | 392 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 15 2008 |
| Externally published | Yes |
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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 journal › Article
}
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 -