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ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ В ПЕДИАТРИИ И ДЕТСКОЙ ХИРУРГИИ
ТЕЗИСЫ
GENETIC INSTABILITY AND CHANGES IN GENE EXPRESSION IN THE OFFSPRING OF MICE AND HUMANS EXPOSED TO RADIATIONS
Nomura Taisei, Ryo Haruko, Adachi Shigeki and Furitsu Katsumi
National institute of Biomedical Innovation, Health and Nutrition, Japan, Osaca
Parental exposure to radiation induces cancer and congenital malformation in mice, in addition to ordinary mutations (Mega mouse experiment), and cancer incidence in F1 was enhanced significantly and drastically by postnatal urethane or TPA treatment (Mutat Res, 1983, etc). Our findings were confirmed by Vorobtsova (1988, 1997) and Lord (1998), and recognized as the first report on radiation induced genomic instability in germ cells (Jeffreys, 2000). Recently, such effects of radiation have been examined by molecular methods using hypervariable tandem repetitive loci (minisatellites, ESTRs and microsatellites). Mutations in tandem repeat loci are mostly detected as gain or loss of repeat unit. We examined microsatellite mutations at D12Mit136, pul67, pi and p5 loci in the mouse germ cell by the nuclear reactor, UTR-KINKI (Kinki University). Identification of microsatellite mutation is precise and objective, because single repeat unit mutations are detectable using capillary sequencer and analyzing software. N5 male mice were exposed to 0.2, 0.4, 0.8 and 1.2 Gy of atomic radiations at the dose rate 0.2 Gy/h of neutrons and 0.2 Gy/h of gamma-rays. Irradiated N5 males were mated with N5 un-irradiated females, and microsatellite mutations were assayed in F1 offspring. PCR products of tail DNA from F1 offspring were analyzed by capillary sequencer (3010x/, Applied Biosystems) and software (GeneMapper, Applied Biosystems), and cancer and malformations were examined later. Microsatellite mutations increased significantly in a dose dependent manner after spermatogonial irradiation, and significant increase of leukemia was also observed dose dependently, although there was no direct link between mutation and leukemia. Preconceptionally irradiated offspring were hypersensitive to phenobarbital, resulting in significantly high incidence of hepatoma. Microsatellite mutations were also induced in the offspring by parental X-ray exposure. Mutations transmit to next generation by Menderian inheritance, and surprisingly, mutations at 3 of 4 loci are accumulated in 2 lines of cancer-prone descendants (up
to F58).
In human populations, microsatellite mutations were not detected significantly in the children of radiation exposed liquidators in Belarus (<50mSv) after Chernobyl accident and those of A-bomb survivors (av. 1.56 Gy) in Hiroshima and Nagasaki, as minisatellite mutations were not. Now, we are examining microsatellite mutations in the children of residents exposed to radionuclides at highly contaminated area near nuclear-bomb test site (Semipalatinsk) and
planning to examine those in highly contaminated area in Russia.
Changes in gene expression also transmitted to further generation in cancer-prone descendants of mice exposed to radiations.
Supported by MEXT Japan, Space Forum, and Russia-Japan Bilateral Joint Research (JSPS-RFBR)
HEALTH CONDITION OF CHILDREN AFTER THE FUKUSHIMA NUCLEAR ACCIDENT AND THE ACTUAL PROBLEM
Yoshida Y, Futagami K.
Chernobyl Health Survey and Health-care Support for the Victims-Japan Women's Network, Tokyo, Japan
Introduction. Four years has passed after the accident at the Fukushima-1 NPP. Concerning the thyroid cancer, Japanese experts assumed, even if radiation effect exists, the first three years after the accident it would not appear.
The results. During these 2 years, the ultrasonic inspection of thyroid gland of children was carried out as the preliminary investigation, and about 300,000 children (81.5% of the subjects in Fukushima) had this inspection. As a result, 112 cases of thyroid cancer or suspected ones were revealed (male vs. female = 38:74, range of age at the accident: 6-18). In April 2014 the full scale inspection started. In this second phase, the result showed newly 15 cases of thyroid cancer or suspected ones in 148,000 inspections by the end of March 2015 (M:F=6:9, age:6-18). Initially it was explained by the experts that the large number of children of thyroid cancer found in Fukushima Prefecture was due to the detailed examination; that is, "Screening effect". But now this assessment was changed to: "This high prevalence of thyroid cancer cannot be explained only by the screening effect." However, because there is almost no reliable data for individual dose to thyroid gland, currently it can neither recognize the causal relation of radiation and cancer, nor deny the relationship. It is required to establish effective health care system while continuing and expanding the investigation. Except the research of thyroid cancer, Governor of Fukushima prefecture has carried out the general health check (height, weight, blood test and biochemical check) to the evacuated children.
Conclusion. Official result tells that there is no large change in the mean value of those data among various age groups for the first three years. The similar health check has not been performed to those living in the contaminated areas. Concerning the pregnancy outcome, principally it is made by questionnaire to corresponding women. Generally the health care and research program after the nuclear accident is insufficient in Japan. The most critical problem is that there is no definition of affected people yet.
РОССИЙСКИЙ ВЕСТНИКПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 4, 2015
