Effects of Proton Radiation Dose, Dose Rate and Dose Fractionation on Hematopoietic Cells in Mice

Abstract

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05–0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

Biological effects of space radiation and development of effective countermeasures

“…However, the difference among animals irradiated with the five fractionated doses, or in a single dose at low or high dose rate, did not reach statistical significance at any of the doses evaluated, and neither the WBC counts nor the lymphocyte counts in the animals irradiated with 2 Gy 1-GeV protons in the five fractionated doses, or in a single dose at low or high dose rate, were significantly different from the animals irradiated with 2 Gy of 51.24-MeV protons administered at a low dose rate (5–7 cGy/minute), although they were all significantly below the control WBC and lymphocyte counts in sham irradiated animals. These results suggest that the effect of proton irradiation on the WBC and lymphocyte counts in the irradiated mice is not altered by dose fractionation, dose rates or proton energy in the ranges evaluated (137). …”

“…The changes in peripheral leukocytes in animals post-irradiation have been evaluated in ICR mice irradiated with 225-kVp X-rays (132), γ-rays from 60 Co (133) or 137 Cs (134–136), protons with energies of 50-MeV (133), 51-MeV (137), 70-MeV (133), 74-MeV (134, 135), 78.4 MeV (138) and 1-GeV protons (137, 139) as well as protons with eight different energies between 31 and 75 MeV and simulated SPE protons with energies between 30 and 150 MeV (140). The changes in peripheral leukocytes have also been examined in ferrets irradiated with 60 Co or 137 Cs γ-rays and 110-MeV protons (141, 142) and Yucatan minipigs irradiated with 6-MeV electrons (130), 6+12-MeV electrons and SPE protons (143, 144).…”

“…In a separate study performed with male ICR mice aged 4–5 weeks, exposure to 1 GeV proton radiation administered in a single dose at low (5 cGy/minute) or high (50 cGy/minute) dose rates, or in five fractionated doses at the low dose rate resulted in significant and dose dependent decreases in peripheral WBC and lymphocyte counts at 24 hours post-irradiation (137). However, the difference among animals irradiated with the five fractionated doses, or in a single dose at low or high dose rate, did not reach statistical significance at any of the doses evaluated, and neither the WBC counts nor the lymphocyte counts in the animals irradiated with 2 Gy 1-GeV protons in the five fractionated doses, or in a single dose at low or high dose rate, were significantly different from the animals irradiated with 2 Gy of 51.24-MeV protons administered at a low dose rate (5–7 cGy/minute), although they were all significantly below the control WBC and lymphocyte counts in sham irradiated animals.…”

Acute hematological effects in mice exposed to the expected doses, dose-rates, and energies of solar particle event-like proton radiation

“…Previous reports on blood cell counts after proton radiation exposure include 1 GeV proton exposures, resulting in decreased white blood cell (WBC) and lymphocyte counts 24 hours after exposure (Wambi et al , 2009, Ware et al , 2010), as well as 24 hours after 70 MeV proton exposure (Maks et al , 2011) and 36 hours after 70 MeV proton exposure (Gridley et al , 2011, Luo-Owen et al , 2012). Blood cell counts in mice remained decreased 4 days and 21 days after exposure to 230 MeV protons (Gridley et al , 2008).…”

Effects of in Vivo Proton Irradiation on Mouse T and B Lymphocytes

“…The effects include alterations in cell number, leukocyte subpopulation frequencies, cytokine production, and antibody production. While the large majority of these results were obtained exposing cells and animals to X or  rays, data on the effects of exposure to protons are still limited [2][3][4][5][6][7]. Weakening of the immune system might represent a serious threat for astronauts as it could expose them not only to the action of genuine pathogens but it could also allow the opportunistic pathogens or latent virus to infect the host.…”