Cytotoxic and cell cycle effects in human neuronal progenitor cells exposed to 1 GeV/n Fe ions

Abstract

With space missions of expanding durations, astronauts will be exposed to increasing amounts of high linear energy transfer heavy ion radiation. One of the potential risks for humans traveling beyond the Earth’s magnetic fields is radiation induced central nervous system damage because these post-mitotic cells cannot replenish themselves. Although neuronal progenitor cells offer hope to replace dead or damaged neurons, very little is known about the effects of heavy ion radiation on them. Thus, we utilized a cloned line of human neuronal progenitor (NT2) cells as a model and measured their responses to irradiation with 1 GeV/nucleon 56Fe 26+ ions. Numerous parameters of radiation toxicity, such as cell detachment, necrosis and apoptosis were induced in both time and dose dependent manners. The highest effect in each case was detected 48 h post-irradiation, and a dose as small as 10 cGy resulted in statistically significant increases in all three of these measurements. In addition, cell cycle analysis revealed that NT2 cells underwent a G2 phase specific cell cycle delay within 6 h after irradiation, and that this response was transient. These results emphasize the importance of determining how human neuronal progenitor cells respond to high linear energy transfer heavy ion radiation.