Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

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.

Chronic irradiation with low-dose-rate 137Cs-γ rays inhibits NGF-induced neurite extension of PC12 cells via Ca2+/calmodulin-dependent kinase II activation

“…The findings of the present study indicated that low-dose-rate 137 Cs-γ irradiation results in clear inhibition of NGF-induced neurite extension, consistent with the findings of previous reports [ 1 , 2 ]. Furthermore, our results revealed that activation of Rac 1 (a protein that induces neurite extension) is influenced by the irradiation-induced activation of CaMKII, independent of the ERK and Akt pathways.…”

“…The effects of low-dose or low-dose-rate irradiation on neuronal cells have drawn increasing attention in recent years. Research has indicated that chronic irradiation with low-dose-rate 137 Cs-γ rays inhibits the differentiation of human neural progenitor cells in a dose-dependent manner [ 1 ]. Furthermore, such chronic irradiation has been shown to influence the expression of proteins associated with cell adhesion, apoptosis, and metabolism, among other functions [ 1 ].…”

“…Research has indicated that chronic irradiation with low-dose-rate 137 Cs-γ rays inhibits the differentiation of human neural progenitor cells in a dose-dependent manner [ 1 ]. Furthermore, such chronic irradiation has been shown to influence the expression of proteins associated with cell adhesion, apoptosis, and metabolism, among other functions [ 1 ]. Similarly, additional studies have reported that low-dose or low-dose-rate 137 Cs-γ radiation inhibits neuronal differentiation of neuroblastoma and neural stem–like cells by inhibiting the expression of proteins associated with cell cycle and cell proliferation [ 2 ].…”

Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior

“…Low-dose radiation effects were previously shown to cause aberrant gene expression in various cells and tissues (Luzhna and Kovalchuk, 2014 ; Sokolov et al, 2015 ; Katsura et al, 2016 ; Sokolov and Neumann, 2016 ). Therefore, we proceeded to analyze the global gene expression profiles of the hippocampus and PFC tissues of control and scatter-exposed male and female rats.…”

Response of neural stem cells to ionizing radiation

“…Moreover the DNA double strand breaks and apoptosis were induced in the ventricular and subventricular zones of mouse embryo [16]. It was also shown that 496 mGy of irradiation caused a significant decrease in the MAP-2 positive cells and neurite length [17]. Thus understanding of the differences between effects induced by different doses and dose-rates of radiation and the impact they may have on neuronal cancer stem cells is crucial for properly predicting the risks of low-dose radiation on the NSC potential to differentiate.…”