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The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model

Jenine K. Sanzari
Jenine K. Sanzari
, 
X. Steven Wan
X. Steven Wan
, 
Gabriel S. Krigsfeld
Gabriel S. Krigsfeld
, 
Andrew J. Wroe
Andrew J. Wroe
, 
Daila S. Gridley
Daila S. Gridley
 et 
Ann R. Kennedy
Ann R. Kennedy
   | 01 juil. 2013
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Article Category: Research Article
Publié en ligne: 01 juil. 2013
Pages: 79 - 94
DOI: https://doi.org/10.2478/gsr-2013-0007
© 2013 Jenine K. Sanzari et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1.

Variance analysis of white blood cell (WBC) results. Variance analysis was performed to determine which experimental factor(s) significantly affected the WBC counts in the animals 3 hours after irradiation (A) or 48 hours after radiation exposure (B). Radiation type (γ-rays vs. protons) did not significantly affect the overall WBC counts after radiation exposure whereas the dose rate did have an effect at 3 hour post-exposure, and total dose also contributed significantly to WBC count changes in the irradiated animals at both 3 hours and 48 hours after exposure. Note: the x-axes labels are included at the top of each panel, i.e., Radiation, Dose Rate, or Dose.
Variance analysis of white blood cell (WBC) results. Variance analysis was performed to determine which experimental factor(s) significantly affected the WBC counts in the animals 3 hours after irradiation (A) or 48 hours after radiation exposure (B). Radiation type (γ-rays vs. protons) did not significantly affect the overall WBC counts after radiation exposure whereas the dose rate did have an effect at 3 hour post-exposure, and total dose also contributed significantly to WBC count changes in the irradiated animals at both 3 hours and 48 hours after exposure. Note: the x-axes labels are included at the top of each panel, i.e., Radiation, Dose Rate, or Dose.

Figure 2.

Dose-response curves for WBC in animals after irradiation. The WBC count results obtained 3 hours after irradiation at HDR (A) or LDR (B) or 48 hours after irradiation at HDR (C) or LDR (D) were determined by a non-linear regression analysis using a linear quadratic model. Statistically significant dose responses were observed for HDR and LDR γ-rays and protons at both time points except for LDR protons at 3 hours after irradiation.
Dose-response curves for WBC in animals after irradiation. The WBC count results obtained 3 hours after irradiation at HDR (A) or LDR (B) or 48 hours after irradiation at HDR (C) or LDR (D) were determined by a non-linear regression analysis using a linear quadratic model. Statistically significant dose responses were observed for HDR and LDR γ-rays and protons at both time points except for LDR protons at 3 hours after irradiation.

Figure 3.

Variance analysis of neutrophil results. Variance analysis was performed to determine which experimental factor(s) significantly affected the neutrophil count in animals 3 hours after irradiation (A) or 48 hours after radiation exposure (B). Radiation type (γ-rays vs. protons) did not significantly affect the overall neutrophil counts after radiation exposure whereas the dose rate did have an effect at 3 hour post-exposure, but not 48 hours post-exposure. Lastly, the total dose did contribute significantly to neutrophil count changes in the irradiated animals at both 3 hours and 48 hours after exposure. Note: the x-axes labels are included at the top of each panel, i.e., Radiation, Dose Rate, or Dose.
Variance analysis of neutrophil results. Variance analysis was performed to determine which experimental factor(s) significantly affected the neutrophil count in animals 3 hours after irradiation (A) or 48 hours after radiation exposure (B). Radiation type (γ-rays vs. protons) did not significantly affect the overall neutrophil counts after radiation exposure whereas the dose rate did have an effect at 3 hour post-exposure, but not 48 hours post-exposure. Lastly, the total dose did contribute significantly to neutrophil count changes in the irradiated animals at both 3 hours and 48 hours after exposure. Note: the x-axes labels are included at the top of each panel, i.e., Radiation, Dose Rate, or Dose.

Figure 4.

Dose-response curves for neutrophils in animals after irradiation. The neutrophil count results obtained 48 hours after irradiation at HDR (A) or LDR (B) were analyzed by a non-linear regression analysis using a linear quadratic model. Statistically significant dose responses were observed for HDR and LDR γ-rays and protons.
Dose-response curves for neutrophils in animals after irradiation. The neutrophil count results obtained 48 hours after irradiation at HDR (A) or LDR (B) were analyzed by a non-linear regression analysis using a linear quadratic model. Statistically significant dose responses were observed for HDR and LDR γ-rays and protons.

Figure 5.

Variance analysis of lymphocyte results. Variance analysis was performed to determine which experimental factor(s) significantly affected the lymphocyte counts in irradiated animals 3 hours (A) or 48 hours (B) after exposure. Radiation type (γ-rays vs. protons) and dose rate did not significantly affect the overall lymphocyte count after radiation exposure, whereas the total dose contributed significantly to lymphocyte count changes in the irradiated animals. Note: the x-axes labels are included at the top of each panel, i.e., Radiation, Dose Rate, or Dose.
Variance analysis of lymphocyte results. Variance analysis was performed to determine which experimental factor(s) significantly affected the lymphocyte counts in irradiated animals 3 hours (A) or 48 hours (B) after exposure. Radiation type (γ-rays vs. protons) and dose rate did not significantly affect the overall lymphocyte count after radiation exposure, whereas the total dose contributed significantly to lymphocyte count changes in the irradiated animals. Note: the x-axes labels are included at the top of each panel, i.e., Radiation, Dose Rate, or Dose.

Figure 6.

Dose-response curves for lymphocytes in animals after irradiation. The lymphocyte count results obtained from animals at 3 hours after irradiation at HDR (A) or LDR (B) or 48 hours after irradiation at HDR (C) or LDR (D) were analyzed by a non-linear regression analysis using a linear quadratic model. Statistically significant dose responses were observed for HDR and LDR γ-rays and protons at both time points. It should be noted that a common log scale is used for y-axis, which has visually exaggerated the deviation of the dose response curves from the actual data points at the high end of the radiation dose range.
Dose-response curves for lymphocytes in animals after irradiation. The lymphocyte count results obtained from animals at 3 hours after irradiation at HDR (A) or LDR (B) or 48 hours after irradiation at HDR (C) or LDR (D) were analyzed by a non-linear regression analysis using a linear quadratic model. Statistically significant dose responses were observed for HDR and LDR γ-rays and protons at both time points. It should be noted that a common log scale is used for y-axis, which has visually exaggerated the deviation of the dose response curves from the actual data points at the high end of the radiation dose range.

Effective doses of γ-rays and protons to decrease blood cell count by 10% (ED10), 50% (ED50), and 90% (ED90)

Cell Type Dose Rate Time after Irradiation Effective dose (and 95% CI) for γ-rays Effective dose (and 95% CI) for protons
ED10 ED50 ED90 ED10 ED50 ED90
WBCs High 3 hours 0.41(0.14 – 0.67) 1.87(0.66 – 3.10) 4.21(1.48 – 6.95) 0.32(0.18 – 0.46) 2.10(1.17 – 3.03) 6.96(3.87 – 10.06)
Low 0.91(0.09 – 1.75) 6.05(0.59 – 11.50) 20.09(1.97 – 38.21) NM NM NM
High 48 hours 0.13(0.09 – 0.17) 0.81(0.55 – 1.08) 2.50(1.70 – 3.30) 0.08(0.06 – 0.11) 0.55(0.37 – 0.72) 1.82(1.24 – 2.39)
Low 0.11(0.07 – 0.15) 0.72(0.47 – 0.96) 2.38(1.57 – 3.19) 0.13(0.09 – 0.18) 0.88(0.59 – 1.18) 2.93(1.94 – 3.91)
Neutrophils High 48 hours 0.31(0.11 – 0.52) 2.04(0.71 – 3.37) 6.51(2.25 – 10.76) 0.18(0.08 – 0.28) 1.19(0.55 – 1.84) 3.95(1.81 – 6.10)
Low 0.27(0.09 – 0.45) 1.79(0.61 – 2.98) 5.96(2.01 – 9.90) 0.42(0.05 – 0.79) 2.12(0.26 – 3.98) 5.03(0.61 – 9.45)
Lymphocyte s High 3 hours 0.05(0.03 – 0.07) 0.33(0.18 – 0.49) 1.11(0.60 – 1.63) 0.05(0.03 – 0.07) 0.32(0.17 – 0.48) 1.07(0.56 – 1.58)
Low 0.06(0.03 – 0.09) 0.41(0.21 – 0.61) 1.36(0.71 – 2.01) 0.06(0.03 – 0.10) 0.41(0.18 – 0.64) 1.35(0.59 – 2.11)
High 48 hours 0.05(0.02 – 0.07) 0.33(0.16 – 0.49) 1.08(0.55 – 1.62) 0.08(0.01 – 0.15) 0.41(0.06 – 0.75) 0.98(0.15 – 1.80)
Low 0.06(0.03 – 0.09) 0.40(0.21 – 0.59) 1.33(0.69 – 1.96) 0.11(0.00 – 0.23) 0.54(0.00 – 1.11) 1.25(0.00 – 2.58)

Relationship between RBE and proton radiation dose for white blood cells (WBCs), neutrophils, lymphocytes.

Cell Type Dose Rate Time after Irradiation 0.75 Gy 1 Gy 2 Gy
RBE 95% CI RBE 95% CI RBE 95% CI
WBCs High 3 hours 2.15 1.51 – 2.79 0.96 0.06 – 1.86 0.62 0.00a – 1.52
Low 4.02 2.25 – 5.79 1.76 0.39 – 3.13 0.59 0.00a – 1.56
High 48 hours 1.60 1.42 – 1.77 1.59 1.34 – 1.84 1.04 0.79 – 1.29
Low 1.19 0.92 – 1.45 0.80 0.59 – 1.00 0.77 0.62 – 0.92
Neutrophils High 48 hours 1.88 1.31 – 2.44 2.04 1.24 – 2.84 1.55 0.75 – 2.35
Low 2.11 1.32 – 2.91 0.62 0.00a – 1.23 0.90 0.46 – 1.34
Lymphocytes High 3 hours 1.10 0.99 – 1.21 1.00 0.84 – 1.15 0.67 0.52 – 0.83
Low 1.41 1.21 – 1.61 0.96 0.81 – 1.12 0.68 0.58 – 0.79
High 48 hours 1.01 0.94 – 1.08 1.06 0.96 – 1.17 0.77 0.67 – 0.88
Low 0.83 0.67 – 1.00 0.99 0.86 – 1.11 0.84 0.74 – 0.93
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