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A Review of Japanese Studies on the Health Effects of Exposure to Low Doses of Ionizing Radiation

by Masahito Kaneko

Introduction

Nuclear power is now recognized as an essential energy source particularly in Japan because of the stable supply of uranium fuel and its ability to resolve such environmental problems as global warming and acid rain. There are now 51 nuclear power reactors in operation and supplying 35 % of the electricity generated in Japan.

However, people are unnecessarily afraid of ionizing radiation and such an extremely low dose limit as 10 microSv/year has been applied to the disposal of low-level solid radioactive wastes. It has been recognized necessary for us to obtain real data on the effects of low doses of ionizing radiation to release the public from unnecessary fear of ionizing radiation.

Presented here is a brief review of animal and human studies on low dose radiation health effects carried out in Japan.


Low Dose-Rate Effects of Radiation in The Induction of Cancer in Mice  
Taisei Nomura (Osaka University)

The study aims at clarifying the Dose-DoseRate-Effectiveness Factor (DDREF). Two different strains of mice, C57BL/6J and C3H/HeJ are used. The experiments (total dose: 6.8 and 2.0 Gy, dose-rate: 0.57 - 0.0002 Gy/min of gamma rays) have demonstrated remarkable reduction of leukemia incidence (DDREF?20 or more) . Additional experiments with the lower total dose of 0.4 Gy are now under way in order to clarify any low dose-rate effects in solid cancers.


Late Effects of Chronic Irradiation by Low Dose-Rate X-Rays on Mice  
Fumiaki Sato (Institute for Environmental Sciences) et al.

Institute for Environmental Sciences is carrying out an experiment on effects of ionizing radiation in mice, particularly with low dose and low dose rate. B6C3F1 mice of both sexes are chronically irradiated with 137Cs gamma-rays. Daily doses are 0.05 mGy/day, 1 mGy/day and 20 mGy/day. The exposure starts from 8 weeks of age and ends after 400 days. A total of 4000 mice are used in the experiment and kept in SPF condition throughout the experiment. All the mice are allowed to complete their life span. Upon death they are thoroughly autopsied. The experiment began in 1996 and will end in 2002.


Tumor Development and Life Shortening by Oral Administration of Tritiated Water in Mice 
0samu Yamamoto (Hiroshima International University) et al.

MKaneko-F1.gif (18925 bytes)Mice were exposed to 3H beta-rays throughout their lives by continuous administration of tritiated drinking water at various dose-rates. The incidence of thymic lymphoma in mice plotted against the dose rate of beta-rays from tritium within the body suggests that there exist the threshold dose-rate (no thymic lymphoma at 7 to 30 cGy/y).

 


Acquisition of Radio-Resistance in Mice Pre-irradiated with Low Dose of Ionizing Radiation
Morio Yonezawa (Osaka Pref. University) et al.

MKaneko-F2.gif (35033 bytes)X-irradiation with 5 – 10 cGy two months before a second exposure to a dose of 8 Gy significantly reduced the death rate in ICR and C57BL strains of mice. Priming dose of 30 – 50 cGy of X-rays induced radio-resistance in mice after two weeks interval.


Suppression of Carcinogenic Process by Low Dose Rate Irradiation
Hiroshi Tanooka, Takeshi Yamada et al. (Central Research Institute of Electric Power Industry)

MKaneko-F3.gif (61006 bytes)Chronic low dose-rate exposure to 137Cs gamma-rays suppressed carcinogenic process in ICR mice with "methylcholanthrene" (chemical carcinogen) injected under the skin of their inguinal region. Among three different dose-rates (A: 0.44 Gy/w, B: 0.16 Gy/w, C: 0.051 Gy/w) applied, the dose-rate B was the optimum.


p53-Dependent Apoptosis Suppresses Radiation-induced Teratogenesis
Toshiyuki Norimura (University of Occupational and Environmental Health) et al.

MKaneko-F4.gif (28551 bytes)After exposure to 2 Gy of X-rays (450 mGy/min) on day 9.5 of gestation, p53 (-/-) mice showed a 70 % incidence of anomalies and a 7 % incidence of deaths, whereas p53 (+/+) mice had a 20 % incidence of anomalies and a 60 % incidence of deaths. After X-irradiation the frequency of dying cells by apoptosis was greatly increased in tissues of the p53 (+/+) fetuses but not at all in those of the p53 (-/-) fetuses. Mammals are protected from radiation-induced injury by two mechanism, p53-dependent apoptotic tissue repair in addition to well known DNA repair.

Total 2 Gy of low dose rate (1.2 mGy/min) exposure to X-rays could not induce malformation in p53 proficient mice. When concerted DNA repair and apoptosis functions efficiently, there is a threshold dose-rate for radiation-induced malformations.


Epidemiological Study of Residents in High Natural Background Radiation Areas
Tsutomu Sugahara (Health Research Foundation) et al.

Epidemiological studies on the residents in Yangjiang district of Guandong province, China are jointly carried out by Chinese and Japanese scientists since 1992.

Data from 1979 to 1995 showed no increased cancer mortality (Relative Risk: 0.99, 95% CI: 0.86 - 1.14), although higher frequency of chromosome aberrations such as dicentrics have been observed among residents in high background radiation areas.

Cooperation with Indian scientists in the epidemiological study of residents in much higher background radiation areas in Kerala district, India, began in 1998. Investigation of setting study cohorts, possible confounding factors, registration of cancer incidence and environmental radiation surveillance started.


Epidemiological Study on Nuclear Industry Workers in Japan
Institute of Radiation Epidemiology, Radiation Effects Association

The first analysis of the mortality of the Japanese nuclear industry workers for the period from 1986 to 1992 demonstrated no evidence of any effect of low-level radiation upon health, particularly upon the cancer mortality. ( The study population: 114,900 male workers, mean cumulative dose of 13.9 mSv, average follow-up period of 4.6 years and 1,758 deaths including 661 malignant neoplasms)

The findings of the second analysis will be published in the nearest future. About 180,000 workers, including more than 5,000 deaths, will be analyzed.


Discussion

ALARA (as low as reasonably achievable) principle based on the "Linear No-Threshold Hypothesis (LNTH)" has significantly contributed to keep radiation exposures of workers and members of the public low. On the other hand, the LNT has been interpreted to mean that "Even a minute amount of radiation is dangerous" and it has produced, or at least increased "Radiophobia." This has made it difficult to fully enjoy the beneficial uses of radiation, to site nuclear power plants and to dispose of radioactive wastes. It may not be justified to spend tremendous amounts of natural and human resources to further reduce trivial amount of exposure doses.

International cooperation of scientists and radiation safety specialists is essential for the achievement of reasonable radiation protection for the benefit of human beings.


References

NOMURA, T., 1999, Personal Communication

SATO, F., "Experimental Study on Late Somatic Effects by Continuous Irradiation", Proceedings of the Thirtieth NIRS Symposium on Radiation Effects, Supplement of Radiological Sciences, Vol. 42, No. 6, 37-42 (1999) (in Japanese)

Yamamoto, O., Seyama, T., Ito, H., Fujimoto, N., "Oral administration of tritiated water in mouse. III: Low dose-rate irradiation and threshold dose-rate for radiation risk", Int. J. Radiat. Biol.,73, 535-541 (1998)

YONEZAWA, M., et al., "Two types of X-ray-induced radio-resistance in mice: Presence of 4 dose ranges with distinct biological effects", Mutat. Res., 358:237-243 (1996)

YONEZAWA, M., et al., "Suppression of p53 and Bax Accumulation after X-irradiation by Small Dose Preirradiation in Radioadaptive Survival Response of C57BL/6 Mice", P-2b-83, Tenth International Congress of IRPA, Hiroshima, Japan (2000)

TANOOKA, H., YAMADA, T., et al. , "Suppression of Carcinogenic Process by Low Dose Rate Irradiation", Program & Abstracts of the Forty-third Annual Meeting of the Japan Radiation Research Society, 3-C-13, August 30 – September 1, 2000, Tokyo, Japan (in Japanese)

NORIMURA, T., NOMOTO, S., KATSUKI, M., GONDO, Y., KONDO, S., "p53-dependent apoptosis suppresses radiation-induced teratogenesis", Nature Med., 2, 577-580 (1996)

KATO, F., OOTSUYAMA, A., and NORIMURA, T., "Dose Rate Effectiveness in Radiation-induced Teratogenesis in Mice", P-2b-80, Tenth International Congress of IRPA, Hiroshima, Japan (2000)

KONDO, S., "Evidence That There are Threshold Effects in Risk of Radiation", Journal of Nuclear Science and Technology, Vol. 36, No. 1, 1-9 (1999)

SUGAHARA, T., "Epidemiological Studies on Low Dose Radiation Exposure", NSRA Primer No. 4 (1998) (in Japanese)

NAIR, K. M., et al., "Population Study in the High Natural Background Radiation Area in Kerala, India", Radiation Research, 152, S145-S148 (1999)

Epidemiological Study Group of Nuclear Workers (Japan), " First Analysis of Mortality of Nuclear Industry Workers in Japan, 1986-1992", Journal of Health Physics, Vol. 32, pp. 173-184 (1997)

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06/14/06