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Radiation and oxidative stress: helping blood stem cells avoid a rough day

An IRCM team (CEA/Inserm) has shown that exposure to low-dose ionizing radiation causes functional losses in human hematopoietic stem cells. Their results, published in Haematologica, suggest the need for complementary care during radiation therapy regimens.

Published on 24 January 2020

The hematopoietic system has long been known for its particularly high radiosensitivity, but how it reacts to the low-dose ionizing radiation delivered during radiation therapy had remained unknown and thus in need of study.

A team from the Laboratory of Hematopoietic Stem Cells and Leukemia (LSHL) tackled that issue and showed that low-dose ionizing radiation (LDIR) exposure does indeed cause functional losses in human hematopoietic stem cells (HSCs).  These latter reside in the bone marrow and give rise to all types of blood cells. HSCs renew themselves as necessary to reconstitute their own population.

In their study, the LSHL researchers isolated human HSCs from umbilical cord blood and exposed them to both low (0.02 Gy) and high (2.5 Gy) cobalt-derived radiation doses. Various in vitro (including colony forming unit (CFU) assays) and in vivo (grafts in immunodeficient mice) evaluations were used to determine the functional properties of those cells. More precisely, their tests, performed in series, were aimed at determining both the differentiation and self-renewal capacities of the human HSCs.

The team's results showed that HSCs exposed to 0.02 Gy do suffer long-term losses of functional properties, notably their ability to generate secondary CFUs in vitro and their capacity for hematopoietic reconstitution in vivo. No DNA alteration or cell death induction was observed. Rather, the team reported that immediately after radiation exposure, the HSCs showed an increase in reactive oxygen species (ROS) and activation of the p38MAPK signaling pathway, which has a known role in maintaining the "stem" properties of those cells. Thereafter, to ensure that the ROS-p38MAPK pathway was indeed responsible for the observed effects, HSCs were treated with either antioxidants or p38MAPK pathway inhibitors before exposure to LDIR. Indeed, the inhibition of that pathway blocked the effect of LDIR on the long-term functional properties of human HSCs.

The results published by the LSHL team show that LDIR has long-term effects on the ability of HSCs to regenerate themselves, due in part to an increase in ROS.

Thus, additional management via the deployment of antioxidants or p38MAPK inhibitors may be necessary during radiation treatments or examinations to protect the hematopoietic system.

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