title: Low-dose total-body γ irradiation modulates immune response to acute proton radiation.
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.
authors.affiliation: Department of Radiation Medicine, Radiation Research Laboratories, Divisions of Biochemistry and Microbiology & Molecular Genetics, Loma Linda University and Medical Center, Loma Linda, California, USA.
authors.forename: Xian
authors.initials: X
authors.lastname: Luo-Owen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
authors.forename: Asma
authors.initials: A
authors.lastname: Rizvi
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology / Q000528:radiation effects; D001835:Body Weight / Q000528:radiation effects; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000276:immunology / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D007109:Immunity / Q000528:radiation effects*; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000528:radiation effects; D011522:Protons / Q000009:adverse effects*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D011522:Protons; D004247:DNA