title: In vivo space radiation-induced non-targeted responses: late effects on molecular signaling in mitochondria.
abstract: The lack of clear knowledge about space radiation-induced biological effects has been singled out as the most important factor limiting the prediction of radiation risk associated with human space exploration. The expression of space radiation-induced non-targeted effects is thought to impact our understanding of the health risks associated with exposure to low fluences of particulate radiation encountered by astronauts during prolonged space travel. Following a brief review of radiation-induced bystander effects and the growing literature for the involvement of oxidative metabolism in their expression, we show novel data on the induction of in vivo non-targeted effects following exposure to 1100 MeV/nucleon titanium ions. Analyses of proteins by two-dimensional gel electrophoresis in non-targeted liver of cranially-irradiated Sprague Dawley rats revealed that the levels of key proteins involved in mitochondrial fatty acid metabolism are decreased. In contrast, those of proteins involved in various cellular defense mechanisms, including antioxidation, were increased. These data contribute to our understanding of the mechanisms underlying the biological responses to space radiation, and support the involvement of mitochondrial processes in the expression of radiation induced non-targeted effects. Significantly, they reveal the cross-talk between propagated stressful effects and induced adaptive responses. Together, with the accumulating data in the field, our results may help reduce the uncertainty in the assessment of the health risks to astronauts. They further demonstrate that 'network analyses' is an effective tool towards characterizing the signaling pathways that mediate the long-term biological effects of space radiation.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School Cancer Center, Newark, NJ 07103, USA.
authors.forename: Mohit R
authors.initials: MR
authors.lastname: Jain
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Sonia M
authors.initials: SM
authors.lastname: de Toledo
authors.forename: Badri N
authors.initials: BN
authors.lastname: Pandey
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Rabin
authors.forename: Edouard I
authors.initials: EI
authors.lastname: Azzam
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects*; D003359:Cosmic Radiation; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology* / Q000528:radiation effects* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000032:analysis / Q000528:radiation effects; D011839:Radiation, Ionizing; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D013026:Space Flight
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species