Abstract
The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.
Highlights
The effects of low dose radiations on human health have recently attracted considerable attention because of the increasing medical use of ionizing radiation, including interventional radiology and frequent radiological examinations, as well as environmental events, such as atomic power plant accidents[1,2,3]
To identify the effects on neural differentiation and development associated with radiation exposure, three doses of radiation were applied to human neural progenitor cells (hNPCs)
Because the formation of neurospheres from hNPCs requires approximately 3 days, we irradiated them for 72 h (Fig. 1a)
Summary
The effects of low dose radiations on human health have recently attracted considerable attention because of the increasing medical use of ionizing radiation, including interventional radiology and frequent radiological examinations, as well as environmental events, such as atomic power plant accidents[1,2,3]. Many scientists have been suspicious of this finding because of various biases which cannot be excluded in the study It remains to be determined whether less than 100 mGy of radiation exerts an effect on tumorigenesis. Besides the consideration of radiation effects on fetuses, recent studies have revealed that even in the adult brain there are neural progenitor cells in the subgranular zone of the dentate gyrus of the hippocampus as well as SVZ12,13. In mice, total body 100 mGy X-irradiation did not induce Alzheimer’s disease-like pathogenesis or memory impairment, even after 1 or 2 years[17] From these reports, the response of neural progenitor cells to low dose radiation should be further determined. Low-dose radiation tends to induce less p53 accumulation owing to the increased ubiquitination by Mdm[2], the activities of which are cell-type specific. Elucidation of the molecular mechanisms underlying cell-specific radiation sensitivity is underway[26]
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