title: Efficient production of reactive oxygen species in neural precursor cells after exposure to 250 MeV protons.
abstract: The space radiation environment is composed of highly energetic ions, dominated by protons, that pose a range of potential health risks to astronauts. Traversals of these particles through certain tissues may compromise the viability and/or function of sensitive cells, including neural precursors found within the dentate subgranular zone of the hippocampus. Irradiation has been shown to deplete these cells in vivo, and reductions of these critical cells are believed to impair neurogenesis and cognition. To more fully understand the mechanisms underlying the behavior of these precursor cells after irradiation, we have developed an in vitro neural precursor cell system and used it to assess acute (0-48 h) changes in ROS and mitochondrial end points after exposure to Bragg-peak protons of 250 MeV. Relative ROS levels were increased at nearly all doses (1-10 Gy) and postirradiation times (6-24 h) compared to unirradiated controls. The increase in ROS after proton irradiation was more rapid than that observed with X rays and showed a well-defined dose response at 6 and 24 h, increasing approximately 10% and 3% per gray, respectively. However, by 48 h postirradiation, ROS levels fell below controls and coincided with minor reductions in mitochondrial content. Use of the antioxidant alpha-lipoic acid (before or after irradiation) was shown to eliminate the radiation-induced rise in ROS levels. Our results corroborate earlier studies using X rays and provide further evidence that elevated ROS are integral to the radioresponse of neural precursor cells.
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California 94103-0806, USA.
authors.forename: Erich
authors.initials: E
authors.lastname: Giedzinski
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Rola
authors.forename: John R
authors.initials: JR
authors.lastname: Fike
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008928:Mitochondria / Q000528:radiation effects; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects*; D011522:Protons / Q000009:adverse effects*; D051381:Rats; D017382:Reactive Oxygen Species; D013234:Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: D011522:Protons; D017382:Reactive Oxygen Species; D008063:Thioctic Acid