Abstract
Accumulating evidences have indicated that ionizing radiation can cause various effects in the cells that have not absorb radiation energy directly. These effects are now collectively called as non-targeted effects. Although the indirect lethal and mutagenic effects have been well described, its effect on differentiation remains to be determined. Cranial radiation causes dysfunctions of the normal central nervous system (CNS), including cognitive impairment, however, the mechanism is not fully understood. Since the CNS is composed of several types of differentiated cells from neural stem cells (NSCs), one possibility mechanism could be that ionizing radiation affects differentiation process of NSCs. Here, we investigated the indirect effects of local X-irradiation on NSCs differentiation using Nagasaki University X-ray microprobe. NSCs plated on coated-mylar membrane or coated glass slips were cultured at least 72 hours in proliferation-competent medium before irradiation. When NSCs were incubated in a differentiation-competent medium for 7 days, they predominantly differentiated into GFAP-positive astrocytes. Then, NSCs were locally-irradiated and incubated in a proliferation-competent medium. Cells in a targeted area were eliminated by apoptosis, however, the number of GFAP-positive cells was increased in the surrounding unirradiated areas. As NSCs differentiation is regulated by soluble factors, our observation might suggest a role of bystander factors, which are secreted by the targeted cells.
