Project Subjects
Elucidation of the Mechanisms of Low Dose Radiation Effects
Background and Objective
The linear non-threshold (LNT) model, which is the basis of current system for radiological protection,
uses linear extrapolation to estimate the possible risks from epidemiological data at high dose down to low dose,
where there is limited data reliable enough. This model has been a foundation to assert that radiation is harmfuleven at a tiny dose; however, recent studies on the low-dose radiation effects have provided evidence that risks
associated with exposure to low-dose and low-dose-rate radiation are lower than those estimated by the LNTmodel. The accurate estimation of health risks of low-dose radiation should lead to the establishment of reasonable protection criteria supported by the scientiﬁc evidence, and the relief of public anxiety for radiation exposure.
With the epidemiological study in the residents of high background radiation areas, this project has shownthat the effects of long-term low-dose-rate radiation exposure would be lower than those observed in the life spanstudy of A-bomb survivors who were exposed in a minute. To clarify the underlying mechanisms, the project
obtains a series of experimental data in animals and cultured cells. Thus, the scientiﬁc basis for the optimizationof radiological protection standards will be strengthened.

Main results
1. Activation of DNA repair function by low dose radiation
Somatic mutation is considered to initiate cancer development. The frequency of somatic mutations onwings of fruit ﬂies Drosophila melanogaster was analyzed after 0.2 or 1 Gy X-irradiation (Fig. 1). 0.2 Gy irradiation reduced the mutation frequency in the DNA repair-proﬁcient wild-type ﬂies compared with non-irradiatedcounterparts. This result suggests that irradiation in the order of 0.2 Gy enhances the repair of background somaticmutations.
A similar reduction was observed in DNA double-strand break repair-deﬁcient ﬂies, but not in DNA
single-strand break repair-deﬁcient ﬂies. This indicates that 0.2 Gy irradiation activates single-strand break repair
gene that reduces background somatic mutations. Because of an orthologous gene, similar phenomenon may also
occur in humans.
2. Response of non-damaged cells in the vicinity of directly irradiated cells
A radiation-induced bystander response is deﬁned as the response of cells that have not themselves been
directly irradiated, but are in the neighborhood of the irradiated cells. The bystander response may have importantbiological consequences under low dose irradiation conditions where irradiated and non-irradiated cells coexist in the same population. In this study, we examined the dose response for induction of bystander cell killingwhere only 5 cells among 7 x 105 cells were irradiated with microbeam X-rays. We found that the X-ray induced
bystander cell killing effect was not detected at 0.12 Gy (Fig. 2). This was in contrast to the case for charged
particle radiation that has been known to induce bystander cell killing even at a tiny dose.
Other reports

Radiation Research 167: 2 (2007), Radiation Research 170: 3 (2010)24

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Nuclear Technology

FigFig.
1 Doseresponse
for thefor
frequencyof somatic
mutationsin fruit flies.
1 Doseresponse
the frequency
of somaticmutationsin fruit ﬂies
Irradiation
withof X-rays
reducedthe mutation
frequency
the DNA
repair-proﬁcientwild-type
Irradiation
with 0.2
Gy0.2
of Gy
X-raysreducedthe mutation
frequency
in theinDNA
repair-proficientwild-type
FM6FM6 strain
andtheDNA
double-strand
break
repair-deﬁcient
Lig4strain.
Incontrast,
thefrequency
increasedwithdose in thestrain and the DNA double-strand break repair-deficient Lig4 strain. In contrast, the frequency increased with doseDNA
single-strand
break
repair-deﬁcient
XRCC1strain.
Theseresultssuggest
thatsingle-strandbreakrepairfunctionin the DNA single-strand break repair-deficient XRCC1 strain. These results suggest that single-strand breakfor the doseFM6 andand Lig4,
that itsand
activation
by 0.2 Gy by
irradiation
repair accounts
function accounts
for responsethe dose observed
response inobservedin Lig4,
FM6 andthat its activation
0.2 Gy reduces background somatic mutations.
irradiation reduces background somatic mutations.

Fig. 2 Dose response for bystander cell survival as a function of the dose to targeted cellsMicrobeam
X-ray-induced
bystander
cell killing
was notasdetected
at 0.12Gy.dose
Even toat targeted
lower doses,
charged particle
Fig 2 Dose
response for
bystander
cell survival
a functionof thecells
radiation
isknown
todecrease
thebystander
cellsurvival(dottedline).
This
resultsuggeststhat
X-raysand charged
Microbeam X-ray-induced bystander cell killing was not detected at 0.12 Gy. Even at lower doses, charged
particle radiation have a different effect on bystander cell killing at low doses.
particle radiation is known to decrease the bystander cell survival (dotted line). This result suggests that X-rays
and charged particle radiation have a different effect on bystander cell killing at low doses.

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