The radiosensitivity of total and quiescent cell populations in solid tumors to 290 MeV/u carbon ion beam irradiation in vivo

Figures & data

Figure 1.  Cell-survival curves for total tumor cell populations as a function of radiation dose immediately after irradiation and 12 hours after irradiation are shown in the left and right panel, respectively. Open triangles, open squares, solid triangles, and solid squares represent the surviving fractions after irradiation with carbon ion beams having an LET of 18, 43, 50, and 74 keV/µm, respectively. Solid circles represent the surviving fractions after γ-ray irradiation. Bars represent standard errors.

Figure 2.  Dose-response curves of normalized micronucleus (MN) frequency for total and quiescent cell populations as a function of radiation dose immediately after irradiation are shown in the left and right panel, respectively. Open triangles, open squares, solid triangles, and solid squares represent the normalized MN frequencies after irradiation with carbon ion beams having an LET of 18, 43, 50, and 74 keV/µm, respectively. Solid circles represent the normalized MN frequencies after γ-ray irradiation. Bars represent standard errors.

Figure 3.  Dose-response curves of normalized micronucleus (MN) frequency for total and quiescent cell populations as a function of radiation dose 12 hours after irradiation are shown in the left and right panel, respectively. Open triangles, open squares, solid triangles, and solid squares represent the normalized MN frequencies after irradiation with carbon ion beams having an LET of 18, 43, 50, and 74 keV/µm, respectively. Solid circles represent the normalized MN frequencies after γ-ray irradiation. Bars represent standard errors.

Table I.  Relative biological effectiveness of carbon ion beams* compared with γ-rays in total and quiescent populations.

18 keV/µm	43 keV/µm	50 keV/µm	74 keV/µm
<Surviving fraction = 0.05, Based on Figure 1 >
Total tumor cells
Immediately after irradiation
1.45	2.15	2.6	3.2
(1.4–1.5)^#	(2.1–2.2)	(2.5–2.7)	(3.1–3.3)
12 h after irradiation
1.55	2.3	2.75	3.3
(1.5–1.6)	(2.2–2.4)	(2.65–2.85)	(3.2–3.4)
<Normalized micronucleus frequency = 0.25 >
Total tumor cells
Immediately after irradiation (Based on Figure 2)
1.25	1.5	1.9	3.1
(1.2–1.3)	(1.4–1.6)	(1.8–2.0)	(3.0–3.2)
12 h after irradiation (Based on Figure 3)
1.3	1.7	2.35	3.2
(1.25–1.35)	(1.6–1.8)	(2.25–2.45)	(3.1–3.3)
Quiescent tumor cells
Immediately after irradiation (Based on Figure 2)
1.4	1.9	2.45	4.35
(1.35–1.45)	(1.8–2.0)	(2.35–2.55)	(4.2–4.5)
12 h after irradiation (Based on Figure 3)
1.45	1.95	2.6	4.5
(1.35–1.55)	(1.85–2.05)	(2.5–2.7)	(4.35–4.65)

*;The ratio of the radiation dose necessary to obtain each end-point with γ-rays and the radiation dose necessary to obtain each end-point with carbon ion beams.

^#;Numbers in parentheses are 95% confidence limits, determined using standard errors. When the ranges of 95% confidence limits have no overlapping between any two values, the difference between the two values was considered significant (p<0.05).

Table II.  Dose-modifying factors after repair of potentially lethal damage.*

18 keV/µm	43 keV/µm	50 keV/µm	74 keV/µm	γ-Rays
<Surviving fraction = 0.05, Based on Figure 1 >
Total tumor cells
1.15	1.15	1.1	1.05	1.3
(1.1–1.2)^#	(1.1–1.2)	(1.05–1.15)	(1.0–1.1)	(1.2–1.4)
<Normalized micronucleus frequency = 0.25, Based on Figures 2 &3 >
Total tumor cells
1.25	1.2	1.15	1.05	1.35
(1.2–1.3)	(1.15–1.25)	(1.1–1.2)	(1.0–1.1)	(1.25–1.45)
Quiescent tumor cells
1.45	1.3	1.25	1.15	1.6
(1.35–1.55)	(1.2–1.4)	(1.15–1.35)	(1.1–1.2)	(1.45–1.75)

*; The ratio of the radiation dose necessary to obtain each end-point with repair and the radiation dose necessary to obtain each end-point without repair.

^#; Numbers in parentheses are 95% confidence limits, determined using standard errors. When the ranges of 95% confidence limits have no overlapping between any two values, the difference between the two values was considered significant (p<0.05).

Table III.  Dose-modifying factors for quiescent cells relative to total tumor cells.*

18 keV/µm	43 keV/µm	50 keV/µm	74 keV/µm	γ-Rays
<Normalized micronucleus frequency = 0.25 >
Immediately after irradiation (Based on Figure 2)
1.5	1.4	1.3	1.15	1.5
(1.4–1.6)^#	(1.3–1.5)	(1.2–1.4)	(1.1–1.2)	(1.4–1.6)
12 h after irradiation (Based on Figure 3)
1.55	1.5	1.4	1.35	1.7
(1.45–1.65)	(1.4–1.6)	(1.3–1.5)	(1.25–1.45)	(1.6–1.8)

*; The ratio of the radiation dose necessary to obtain each normalized micronucleus frequency in quiescent cells and the radiation dose necessary to obtain each normalized micronucleus frequency in total tumor cells.

^#; Numbers in parentheses are 95% confidence limits, determined using standard errors. When the ranges of 95% confidence limits have no overlapping between any two values, the difference between the two values was considered significant (p<0.05).