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.

FIG. 1

Dose–response effects of proton radiation on WBC counts in irradiated mice. The mice were irradiated with 1 GeV protons in five daily dose fractions at a dose rate of 0.05–0.07 Gy/min or in a single dose at a high (0.5 Gy/min) or low (0.05 Gy/min) dose rate (5–10 mice per group). The WBC counts were determined 24 h after the last radiation exposure. The results were compared among different treatment groups by one-way ANOVA followed by Tukey’s test. The statistical significance of the difference between the sham-irradiated control and each of the irradiated groups is indicated by asterisks (**P < 0.01 and ***P < 0.001 by Tukey’s test). The error bars represent standard errors.

FIG. 2

Dose–response effects of proton radiation on lymphocyte counts in irradiated mice. The mice were irradiated with 1 GeV protons in five daily dose fractions at a dose rate of 0.05–0.07 Gy/min or in a single dose at a high (0.5 Gy/min) or low (0.05 Gy/min) dose rate (5–10 mice per group). The lymphocyte counts were determined 24 h after the last radiation exposure. The results were compared among different treatment groups by one-way ANOVA followed by Tukey’s test. The statistical significance for the difference between the sham-irradiated control and each of the irradiated groups is indicated by asterisks (*P < 0.05, **P < 0.01 and ***P < 0.001 by Tukey’s test). The error bars represent standard errors.

FIG. 3

Comparison of WBC and lymphocyte counts among mice irradiated with 1 GeV and 51.24 MeV protons at a dose of 2 Gy. The mice were irradiated with 1 GeV protons in five daily dose fractions at a dose rate of 0.05–0.07 Gy/min (1-GeV, FD) or in a single dose at a high (1-GeV, HDR) or low (1-GeV, LDR) dose rate or with 51.24 MeV protons in a single dose at a dose rate of 0.05–0.07 Gy/min (51.24–MeV) (5–10 mice per group). The WBC and lymphocyte counts were determined 24 h after the last radiation exposure. The results were compared among different treatment groups by one-way ANOVA followed by Tukey’s test. The statistical significance for the difference between the sham-irradiated control and each of the irradiated groups is indicated by asterisks (***P < 0.001 by Tukey’s test). The error bars represent standard errors.