Low-dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

Radiat Res. 2012 Mar;177(3):251-64. doi: 10.1667/rr2785.1. Epub 2011 Dec 7.

Abstract

Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate γ rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with ⁵⁷Co (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to γ rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to γ rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+ T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with γ radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate γ rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Blood Platelets / immunology
  • Blood Platelets / radiation effects
  • Body Weight / radiation effects
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Cytokines / metabolism
  • DNA / biosynthesis
  • Dose-Response Relationship, Radiation
  • Erythrocytes / immunology
  • Erythrocytes / radiation effects
  • Female
  • Gamma Rays / adverse effects*
  • Immunity / radiation effects*
  • Leukocyte Count
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Organ Size / radiation effects
  • Protons / adverse effects*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / radiation effects
  • Whole-Body Irradiation / adverse effects*

Substances

  • Antibodies
  • CD28 Antigens
  • CD3 Complex
  • Cytokines
  • Protons
  • DNA