Human hematopoietic stem/progenitor cells display reactive oxygen species-dependent long-term hematopoietic defects after exposure to low doses of ionizing radiations.
Journal
Haematologica
ISSN: 1592-8721
Titre abrégé: Haematologica
Pays: Italy
ID NLM: 0417435
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
14
05
2019
accepted:
27
11
2019
pubmed:
30
11
2019
medline:
28
4
2021
entrez:
30
11
2019
Statut:
ppublish
Résumé
Hematopoietic stem cells are responsible for life-long blood cell production and are highly sensitive to exogenous stresses. The effects of low doses of ionizing radiations on radiosensitive tissues such as the hematopoietic tissue are still unknown despite their increasing use in medical imaging. Here, we study the consequences of low doses of ionizing radiations on differentiation and self-renewal capacities of human primary hematopoietic stem/progenitor cells (HSPC). We found that a single 20 mGy dose impairs the hematopoietic reconstitution potential of human HSPC but not their differentiation properties. In contrast to high irradiation doses, low doses of irradiation do not induce DNA double strand breaks in HSPC but, similar to high doses, induce a rapid and transient increase of reactive oxygen species (ROS) that promotes activation of the p38MAPK pathway. HSPC treatment with ROS scavengers or p38MAPK inhibitor prior exposure to 20 mGy irradiation abolishes the 20 mGy-induced defects indicating that ROS and p38MAPK pathways are transducers of low doses of radiation effects. Taken together, these results show that a 20 mGy dose of ionizing radiation reduces the reconstitution potential of HSPC suggesting an effect on the self-renewal potential of human hematopoietic stem cells and pinpointing ROS or the p38MAPK as therapeutic targets. Inhibition of ROS or the p38MAPK pathway protects human primary HSPC from low-dose irradiation toxicity.
Identifiants
pubmed: 31780635
pii: haematol.2019.226936
doi: 10.3324/haematol.2019.226936
pmc: PMC7395291
doi:
Substances chimiques
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2044-2055Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright© 2020 Ferrata Storti Foundation.
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