Radiation Research

Published by: Radiation Research Society

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Radiation Research 169(3):280-287. 2008
doi: 10.1667/RR1155.1

Low-Dose Photons Modify Liver Response to Simulated Solar Particle Event Protons

Daila S. Gridley1ab, George B. Coutrakona, Asma Rizvib, Erben J. M. Bayetaa, Xian Luo-Owena, Adeola Y. Makindeb, Farnaz Baqaib, Peter Kossa, James M. Slatera, and Michael J. Pecautab

aDepartment of Radiation Medicine, Molecular Radiation Biology Laboratories, Loma Linda University and Medical Center, Loma Linda, California 92354

bDepartment of Biochemistry & Microbiology, Loma Linda University and Medical Center, Loma Linda, California 92354

1011 Address for correspondence: Loma Linda University; Chan Shun Pavilion, Room A-1010, 11175 Campus Street; Loma Linda, CA 92354, U.S.A;

Abstract

Gridley, D. S., Coutrakon, G. B., Rizvi, A., Bayeta, E. J. M., Luo-Owen, X., Makinde, A. Y., Baqai, F., Koss, P., Slater, J. M. and Pecaut, M. J. Low-Dose Photons Modify Liver Response to Simulated Solar Particle Event Protons. Radiat. Res. 169, 280–287 (2008).

The health consequences of exposure to low-dose radiation combined with a solar particle event during space travel remain unresolved. The goal of this study was to determine whether protracted radiation exposure alters gene expression and oxidative burst capacity in the liver, an organ vital in many biological processes. C57BL/6 mice were whole-body irradiated with 2 Gy simulated solar particle event (SPE) protons over 36 h, both with and without pre-exposure to low-dose/low-dose-rate photons (57Co, 0.049 Gy total at 0.024 cGy/h). Livers were excised immediately after irradiation (day 0) or on day 21 thereafter for analysis of 84 oxidative stress-related genes using RT-PCR; genes up or down-regulated by more than twofold were noted. On day 0, genes with increased expression were: photons, none; simulated SPE, Id1; photons + simulated SPE, Bax, Id1, Snrp70. Down-regulated genes at this same time were: photons, Igfbp1; simulated SPE, Arnt2, Igfbp1, Il6, Lct, Mybl2, Ptx3. By day 21, a much greater effect was noted than on day 0. Exposure to photons + simulated SPE up-regulated completely different genes than those up-regulated after either photons or the simulated SPE alone (photons, Cstb; simulated SPE, Dctn2, Khsrp, Man2b1, Snrp70; photons + simulated SPE, Casp1, Col1a1, Hspcb, Il6st, Rpl28, Spnb2). There were many down-regulated genes in all irradiated groups on day 21 (photons, 13; simulated SPE, 16; photons + simulated SPE, 16), with very little overlap among groups. Oxygen radical production by liver phagocytes was significantly enhanced by photons on day 21. The results demonstrate that whole-body irradiation with low-dose-rate photons, as well as time after exposure, had a great impact on liver response to a simulated solar particle event.

Received: July 16, 2007; Accepted: November 8, 2007



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FIG. 1. Schematic of the three irradiation regimens. LDR, low-dose, low-dose-rate photon irradiation; sSPE, simulated SPE proton irradiation

FIG. 2. Brief overview of proton beam delivery and control system concept used at LLUMC for simulated SPE proton irradiation. A new beam delivery system was built to achieve the desired energy spectrum and dose rate over the 1-m2 area occupied by the mice. A novel feature was the use of beam deflection scanning magnets similar to those used in advanced forms of proton therapy. A more detailed description of the delivery system and dosimetry is presented in ref. (26)

FIG. 3. Oxygen radical production by phagocytic cells in liver on day 21 postirradiation. Bars represent means ± SEM for 10–14 mice/group. One-way ANOVA for main effect of group, P < 0.001. a: P < 0.05 compared to 0 Gy and simulated SPE (P = 0.081 compared to photons + simulated SPE); b: P < 0.05 compared to photons and photons + simulated SPE (P = 0.070 compared to 0 Gy); c: P < 0.01 compared to simulated SPE. LDR, low-dose, low-dose-rate photon irradiation; sSPE, simulated SPE proton irradiation

table

TABLE 1 Up-regulated Genes on Day 0

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TABLE 2 Down-regulated Genes on Day 0

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TABLE 3 Up-regulated Genes on Day 21

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TABLE 4 Down-regulated Genes on Day 21

Cited by

Jian Tian, Michael J. Pecaut, George B. Coutrakon, James M. Slater, Daila S. Gridley. (2009) Response of Extracellular Matrix Regulators in Mouse Lung after Exposure to Photons, Protons and Simulated Solar Particle Event Protons. Radiation Research 172:1, 30-41
Online publication date: 1-Jul-2009.

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