２ Principal Research Results
Project Research ― Establishment of Optimal Risk Management

Elucidation of the Mechanisms of Low-dose
Radiation Effects

Background andObjective

Main results

The current system for radiation protection has
been established according to the linear nonthreshold (LNT) model, which mainly employs
epidemiological data on human populations
exposed to high-dose/high-dose-rate radiation andwhich uses a linear extrapolation down to the lowdose/low-dose-rate to estimate the possible risks.
Recently, there is emerging evidence indicating thatthe risks associated with exposure to low-doserate radiation that is below that of 10 times higher
than natural background level are lower thanthose estimated by the LNT model. An accurate
estimation of the health risk of low-dose radiation

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This project is undertaken to illustrate that there isno increase in radiation risks at a low-dose-rate, andit aims to decipher underlying mechanisms, throughhuman epidemiological studies in high backgroundradiation areas (HBRAs) and experimental studies inanimals and cultured cells. Thus, the scientific basis
to achieve reasonableness in radiation protection
criteria will be strengthened.

E p id e m i ol og ic a l R e s e a r c h S t u d y o f R e s i d e n t s i n H B R A s i n C h i n a

The results from an epidemiological study of HBRA
residents in Yangjiang, Guangdong Province, China
were published. The group of subjects included
about 32,000 persons aged 30–74 years, andthe follow-up period was extended to 20 years,compared with the previous report. Mean cumulative
radiation doses from natural radiation in the HBR
and control-area* 1 residents were 84.8 mGy and2should lead to the establishment of reasonable
protection criteria supported by scientific evidence,along with the relief of public anxiety regarding
radiation exposure.

21.6 mGy*2, respectively. No significant increasesof excess relative risk were observed for cancer
mortality (Fig. 1), leukemia, or non-cancer mortality(Table 1). These results indicate the possibility thatthe risks associated with prolonged low-dose-rate
exposure would be lower than those estimated by
the LNT model, as with the results of an HBRA studyin India (Fig. 1).

Su p p r e s s i on o f Sp o n t a n e o u s M u t a t i o n b y R a d i a t i o n - i n d u c e d B y s t a n d e r
R e s p on s e

Radiation-induced bystander response is defined
as a response of cells that are not directly targetedby radiation but that are in the vicinity of cells
that have been directly exposed. Due to its nature,it has been often suggested that the number ofcells in which biological effects are induced ishigher than that of the irradiated cells under lowdose and/or low-dose-rate irradiation conditions
where both irradiated and unirradiated cells
coexisted in the same tissue. The aim of this study
is, using the X-ray microbeam irradiation method,
to clarify the relationship between radiationinduced bystander responses and mutagenesis,
one of the requisites of carcinogenesis. Five cells

within 1 × 10 5 cells on a dish were irradiatedwith a series of doses from an X-ray microbeam,and the dose response of the surviving fraction(Fig. 2A) and mutation frequency (Fig. 2B) in the
bystander population was determined. Both thesurviving fraction and the mutation frequency
decreased at doses around 1 Gy. The similarity ofthese behaviors suggests that the enhancement of
bystander cell killing participates in a mechanismthat eliminates the cells having mutagenic DNA
regions, selectively. In other words, biologicaleffects at low-dose regions cannot be enhanced
by bystander response.

*1 The area near the HBRA in which the terrestrial radiation levels are low and the lifestyle is similar to the HBRA.
*2 Unit of absorbed dose; 1 mGy = 1 mSv in this case, as the doses in this study consist of those from external exposure with terrestrial gamma rays.

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Other reports: Tao et al., Health Phys., 2012 and Maeda et al., J.Radiat.Res., 2012

Table 1, Fig. 1: Results of an epidemiological study of HBRA residents in China
No increase of risk with the dose was observed in comparison with the control area. This result is the same as
the Indian study, and it is different from the atomic bomb survivor study, which shows the increase of cancer
risks in proportion with dose. The cumulative dose of each Chinese data point in Fig. 1 was calculated as acenter value of the mGy dose categories of 0–24, 25–49, 50–74, 75–99, 100–124, and 125 and up.

(A)

(B)

Project Research - Establishment of Optimal Risk Management

When both the lower limits (left figures) and upper
limits (right figures) of the 95-percent confidence
intervals (95% CIs) are positive or negative, it canbe concluded that significant effects due to radiation
exposure were detected. No significant effects on themortalities of diseases in the table were shown.

2 Principal Research Results

ERR: Excess Relative Risk, the value of relative risk
minus one; relative risk is the ratio of mortality
in the subject group versus the control group.
ERR/Gy corresponds to the values of the slopesin Fig. 1, indicating an increase of relative risk
per unit dose.

The mutation frequency decreased
significantly from background levels
at doses where the surviving fraction
decreased.

Fig. 2: Suppression of spontaneous mutation by X-ray-induced bystander response(A) Effect of bystander response on the surviving fraction of Chinese hamster V79 cells as a function of
the nuclear-averaged dose in the irradiated cells; the surviving fraction decreased as a result of bystander
response at doses around 1 Gy, but at higher doses, the surviving fraction recovered. (B) Mutation frequency
measured in the same cell populations used in Fig. 2A; the mutation frequency decreased significantly frombackground (0 Gy) levels at doses where the surviving fraction decreased. At higher doses, the mutation
frequency did not become higher than background levels.

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