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On radiation-induced adaptive response in fetal mice: I.. A study at the cellular and whole-body levels
https://repo.qst.go.jp/records/62774
https://repo.qst.go.jp/records/62774f1120cdf-75c8-49e2-b3af-c166c0c9af57
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-10-09 | |||||
| タイトル | ||||||
| タイトル | On radiation-induced adaptive response in fetal mice: I.. A study at the cellular and whole-body levels | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Bing, Wang
× Bing, Wang× Ohyama, Harumi× Tanaka, Kaoru× Shang, Yi× Watanabe, Keiko× Nakajima, Tetsuo× Nenoi, Mitsuru× Hayata, Isamu× 王 冰× 大山 ハルミ× 田中 薫× 尚 奕× 渡辺 恵子× 中島 徹夫× 根井 充× 早田 勇 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Radiation-induced adaptive response is the phenomenon of priming low-dose irradiation-induced resistance to subsequent irradiation at higher doses. As investigations on adaptive response provide important scientific basis for radiation risk estimates and offer significant insight into the novel biological defense mechanisms regarding protection against radiation, study on radiation-induced adaptive response is of great concern for both public health and academic research. It is demonstrated that the radiation-induced adaptive response exists in both procaryotic and eucaryotic cells. For the research work on mammalian systems, most of the studies were performed using cultured cells in vitro. Only a few works were done at the whole body level. Since the data of epidemiological studies in humans are insufficient, the results from animal experiments are extremely important. The in vivo studies using either mouse pre-implantation embryos or rat fetal brain have failed to show any positive data. Using fetal mice in utero, we demonstrated the existence of radiation-induced adaptive response and characterized the experimental conditions for the successful induction. To date, it is known that a variety of physical and biological conditions with respect to both irradiation and irradiated subjects are crucial to the induction of adaptive response. The biological endpoints employed are also of importance to confirmation of the existence or a judgment of the successful induction of adaptive response. Radiation induces high incidences of abnormalities and neonatal death in late organogenesis in mice. As gross malformations in limbs and digits are easy to be judged, prenatal fetal death and digital defects were used as the endpoints in our study. Thus, the radiation-induced adaptive response was judged as a priming low dose radiation-induced reduction of a subsequent high dose radiation-induced fetal death and prenatal digital defects. As the developing limb system in mice is widely used for correlating the initial pathological changes in early limb buds with final digital defects and digital defects were due to an excess induction of p53 dependent apoptosis by the high dose of irradiation, to study the cellular response under an adaptive response, investigation was conducted for the correlation between both the p53 gene status and the radiation-induced apoptosis with the induction of digital defects in fetal mice. In a series of our studies in fetal mice, existence of the radiation-induced adaptive response was demonstrated in both ICR and C57BL strain fetal mice by priming low dose radiation on gestation day 11 prior to a high dose irradiation on gestation day 12. It was found that suppression of the digital defects was correlated to the inhibition of radiation-induced apoptosis in the predigital regions. The efficient priming dose was mouse strain-related, namely, the efficient priming dose for ICR fetal mice was 0.3 Gy while either 0.05 Gy or 0.3 Gy was efficient for induction of an adaptive response in C57BL fetal mice. An adaptive response could not be induced in p53 heterozygous (p53+/-) fetal mice under the same conditions as those used in the p53 wild type (p53+/+) fetal mice. This indicated that both p53 alleles were essential for a successful induction of adaptive response in fetal mice. Furthermore, existence of the dose-rate effect was verified for delivery of the priming dose in ICR fetal mice. Adaptive response was observed within two dose-rate ranges for the same dose of priming irradiation, namely, 0.3 Gy was delivered either from 0.18 to 0.98 Gy/min or from 3.5 to 4.6 Gy/min on gestation day 11, for reduction of the detrimental effect induced by a challenging dose of 3.5 Gy on gestation day12. In the follow-up study on the offspring that survived from high dose induced prenatal death, a high postnatal mortality was observed. In addition, detrimental effects such as postnatal retardation, alteration in adult behavior, and life span shortening were also observed in these survivals. Furthermore, using 30-day survival test and radiation treatment conditions for induction of adaptive response in vivo in adult mice, the responses of the postnatal survivals to the lethal irradiation and to the adaptive response induction were investigated in C57BL mice. A significantly increased radiosensitivity to the killing effect was observed and the adaptive response could not be induced in these offspring. These findings suggested that some tissue damage, which was caused by fetal high dose irradiations, could not be completely repaired although the animals may survive. In summary, the results obtained in this experimental system indicated that radiation-induced adaptive response in fetal mice is due to a complex interplay between dose, dose rate and animal factors such as the strain, developmental stage, and genetic background. A priming low dose of irradiation, if delivered at certain restrictive conditions, i.e., at the efficient dose and dose rate, and on the specific developmental stage, could rescue some fetal mice from prenatal death induced by the subsequent high dose of irradiation, while the postnatal survivals are not as healthy as those non-irradiated controls, showing significant alterations in physiological maturation, neuroreflex, behavior, and lifespan. The postnatal survivals did not response to radiation the same as the control non-irradiated animals. This work was supported in part by the Budget for New Nuclear Crossover Research from the Ministry of Education, Culture, Sports, Sciences and Technology, Japan. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | NIRS International Symposium on Visualization of Radiation Response at the Molecular and Cellular Levels | |||||
| 発表年月日 | ||||||
| 日付 | 2007-03-13 | |||||
| 日付タイプ | Issued | |||||
