Principal Research Results

Long Term Effects of Low Dose-rate Gamma Radiation on Mouse
Hematopoietic System
Background
Hematopoietic system is known as one of the most radio-sensitive tissues in the mammalian body and transient reduction of
the number of peripheral blood cells can be detected by around 0.5 Gy (almost 500 times higher than natural background radiation peryear) of acute exposure. However, there is little information about a variation in the number of peripheral blood cells, especiallyhematopoietic stem cells exposed to low dose-rate (chronic) long term whole body irradiation. Therefore, it is expected to study doserate effects by low dose-rate irradiation on hematopoietic system.

Objectives
To evaluate the effects of low dose-rate irradiation on mouse hematopoietic system, mice were irradiated with gamma-ray inthe low dose rate long term irradiation facility and the number of peripheral blood cells (red blood cells and white blood cells) andhematopoietic stem cells were studied.

Principal Results
1. Dose rate effect in terms of the number of blood cells.
Mice were irradiated with 0.5 Gy at 0.5 Gy/min as a high dose rate or at 1.2 mGy/hr as a low dose rate. Both of the numbersof white and red blood cells were significantly decreased at a high dose-rate while such a decrease was not observed at a low dose-rate(Fig.1).
2. Long term variations of the number of blood cells by low dose rate irradiation
Chronic low dose rate irradiation for 200 days (5 Gy of accumulate dose) induced a transient reduction of the number ofwhite blood cells in an early stage; however, it was recovered to as much as control level by further irradiation. Red blood cells also
reduced slightly by 40 days irradiation but they were finally recovered to as much as control level (Fig.2).
3. Frequency of hematopoietic stem cells.
Low dose-rate gamma-ray was exposed to mouse for 3, 5, 9 or 26 weeks and the abundance of hematopoietic stem cells inbone marrow was studied. Significant differences were not shown between irradiated group and non-irradiated control (Table 1).
The results described above indicated that the effects on the number of peripheral blood cells were quite different in the caseof low dose rate or high dose rate. In particular, the ability of hematopoiesis was maintained after irradiation about 10 times higher
than minimum dose (0.5 Gy) which reduces the number of blood cells in the case of low dose rate.

Future Developments
We will study the mechanism of differentiation of hematopoietic stem cells into peripheral blood cells induced by further
irradiation and research the limit dose of influence.
Main Researcher : Kensuke Otsuka,
Research Scientist, Low Dose Radiation Research Center, Nuclear Technology Research Laboratory
ReferenceK. Otsuka, et al., 2006, “Effects for hematopoietic stem cells and peripheral blood by low dose-rate irradiation.” CRIEPI Report
L05016 (in Japanese)42

C. Harmonization of energy and environment

1200

*

Red blood cells (x 10000 / l)White blood cells (x 100 / l)

150

120

906030**

1000
800
600
400
200

00
high
dose-rate

controllowdose-rate

controlhighdose-rate

low
dose-rate

Whole body gamma-irradiation (0.5Gy) was performed at 0.5 Gy/min as ahigh dose rate or 1.2 mGy/hr as a lowdose rate.
Both cell numbersreduced significantly after high dose
rate irradiation while low dose rate
did not induce any reduction.
(*: P<0.01,**: P<0.001,TukeyKramer method)

Fig.1 Dose rate effect in terms of blood cell number

1200

Red blood cells (x 10000 / l)White blood cells (x 100 / l)

150

120

9060301100
1000

0900

*800
700
600

050100

150

200

0250

50

100

150200250

Irradiation period (days)

non-irradiated control,
1.2mGy/hr irradiated. White bloodcells slightly decreased in the earlystage and red blood cells decreasedby 40 days continuous irradiation.
However, both cells recovered to as
much as non-irradiated control levelin the long term.
(*: P<0.05, Student’s t-test)

Fig.2 Variation in cell number among low dose-rate longterm irradiation

Table 1 Abundance of hematopoietic stem cells in mouse bone marrow

Abundance of hematopoietic stem cells (%)
Control
Low dose-rate irradiatedP value

0.58

0.007 ± 0.001

0.004 ± 0.001

0.1250.970.006 ± 0.001

0.003 ± 0.001

0.1191.740.012 ± 0.001

0.010 ± 0.000

0.18265.02

0.018 ± 0.009

0.021 ± 0.018

0.69

Irradiation period(weeks)(Gy)
Accumulated dose3

The abundance of hematopoietic stem cells in mouse bone marrow irradiated low dose rate long term (3, 5, 9 or
26 weeks) did not show significant differences compared with non-irradiated control in any irradiation periods(*: P value, Student’s t-test)

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