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Tian J.,Radiation Research Laboratories | Zhao W.,Loma LindaUniversity | Tian S.,Wake forest University | Slater J.M.,Radiation Research Laboratories | Deng Z.,Loma LindaUniversity
Radiation Research | Year: 2011

The goal of this study was to compare the effects of acute 2Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/lowdose-rate c rays (0.01 Gy at 0.03 cGy/h), on 84 genes involvedin stem cell differentiation or regulation in mouse lungs ondays 21 and 56. Genes with a ©1.5-fold difference inexpression and P , 0.05 compared to 0 Gy controls areemphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were alsocompared. Overall, striking differences were present betweenprotons and photons in modulating the genes. More geneswere affected by protons than by photons (22 compared to 2and 6 compared to 2 on day 21 and day 56, respectively)compared to 0 Gy. Preirradiation with low-dose-rate c raysenhanced the acute photon-induced gene modulation on day21 (11 compared to 2), and all 11 genes were significantlydownregulated on day 56. On day 21, seven genes (aldh2,bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulatedin response to most of the radiation regimens. Immunoreactivityof Clara cell secretory protein was enhanced by allradiation regimens. The number of alveolar type 2 cellspositive for prosurfactant protein C in irradiated groups washigher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P , 0.05). Taken together, these resultsshowed that acute photons and protons induced differentgene expression profiles in the lungs and that pre-exposure tolow-dose-rate c rays sometimes had modulatory effects. Inaddition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation. © 2011 byRadiation Research Society.

Pecaut M.J.,Radiation Research Laboratories | Pecaut M.J.,Loma Linda University | Gridley D.S.,Radiation Research Laboratories | Gridley D.S.,Loma Linda University
In Vivo | Year: 2011

Although there is a large body of evidence indicating that radiation can have a dramatic impact on both immune and brain junction, there is very little known about its effect on communication between these critical two systems. In this study, mice were exposed to head-localized irradiation with 5 Gy 56Fe26+ ions and assessed for immune function. Mice were inoculated with lipopolysaccharide 37-38 days post-irradiation. Subsets of mice were euthanized 1, 7, or 14 days later. Radiation significantly impacted the response to an immune challenge in terms of splenic and circulating leukocyte counts and lymphocyte distributions; the effect was especially pronounced on granulocytes and B-cells (p<0.05). However, there were no interactions in spontaneous or mitogen-induced blastogenesis of activated T-cell proportions, brain interleukin-1ß, or circulating corticosterone levels. These data demonstrate that head-localized iron ion radiation modified the peripheral response to a potent bacterial component associated with septic shock.

Haerich P.,Loma Linda University | Eggers C.,Veterans Administration San Diego Healthcare System | Pecaut M.J.,Radiation Research Laboratories | Pecaut M.J.,Loma Linda University
Radiation Research | Year: 2012

With the increased international emphasis on manned space exploration, there is a growing need to understand the impact of the spaceflight environment on health and behavior. One particularly important aspect of this environment is low-dose radiation. In the present studies, we first characterized the γ-and proton-irradiation dose effect on acoustic startle and pre-pulse inhibition behaviors in mice exposed to 05 Gy brain-localized irradiation, and assessed these effects 2 days later. Subsequently, we used 2 Gy to assess the time course of γ-and proton-radiation effects on startle reactivity 08 days after exposure. Exposures targeted the brain to minimize the impact of peripheral inflammation-induced sickness behavior. The effects of radiation on startle were subtle and acute. Radiation reduced the startle response at 2 and 5 Gy. Following a 2-Gy exposure, the response reached a minimum at the 2-day point. Proton and γ-ray exposures did not differ in their impact on startle. We found there were no effects of radiation on pre-pulse inhibition of the startle response. © 2012 by Radiation Research Society.

Mehrotra S.,Radiation Research Laboratories | Pecaut M.J.,Loma Linda University | Gridley D.S.,Radiation Research Laboratories | Gridley D.S.,Loma Linda University
In Vivo | Year: 2013

Background/Aim: We previously found that minocycline enhanced the levels of several leukocyte populations and had the capacity to induce secretion of certain cytokines early after irradiation. In the current study we further determined the drug's effect on hematopoietic recovery. Materials and Methods: Minocycline was injected intraperitoneally into C57BL/6 mice for 5 days, beginning immediately before exposure to 60Co γ-rays (1, 2, 3 Gy). Thirty-two days post-irradiation, spleen and blood were collected to quantify cell populations, cytokines in splenic T-cell supernatants after anti-CD3 activation, and chromosomic status based on spectral karyotyping. Results: While radiation resulted in significantly lower B-cell counts at 3 Gy in both blood and spleen, minocycline treatment increased the counts and/or percentages of splenic B-cells at 2 Gy and 3 Gy. In spleen supernatants, the drug-alone increased the levels of cytokines, including interleukin-1α (IL-1α) and IL-6 that are radioprotective, as well as granulocyte- macrophage colony-stimulating factor (GM-CSF) and G-CSF that accelerate neutrophil recovery. In addition, minocycline suppressed the production of interferon-γ that can prevent hematopoiesis. Dose-dependent radiation-induced chromosomic abnormalities were present in splenic leukocytes. Conclusion: The data indicate that minocycline exerts a relatively long-term effect on parameters that influence hematopoietic recovery. Further testing of this drug as a countermeasure for acute radiation syndrome, is necessary to determine its full potential.

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