Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells.
The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-kappaB) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min(-1), the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of (137)Cs gamma rays (10 mGy min(-1)). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or (137)Cs gamma rays, delivered at 10 mGy min(-1), was similar. Although statistically significant levels of NF-kappaB activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p < 0.05 or <0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min(-1) induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.
Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691, USA. krithidech@notes.sunysb.edu
Kanokporn Noy
KN
Rithidech
Paiboon
P
Reungpatthanaphong
Louise
L
Honikel
Adam
A
Rusek
Sanford R
SR
Simon
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000528:radiation effects*; D016207:Cytokines / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011522:Protons
D016207:Cytokines; D016328:NF-kappa B; D011522:Protons