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Radiation-induced adaptive response in fetal mice: A microarray study
https://repo.qst.go.jp/records/61628
https://repo.qst.go.jp/records/6162835ea150c-ee27-49ff-9239-a1965e89f293
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2006-07-05 | |||||
| タイトル | ||||||
| タイトル | Radiation-induced adaptive response in fetal mice: A microarray study | |||||
| 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 |
Vares, Guillaume
× Vares, Guillaume× Bing, Wang× Nenoi, Mitsuru× Nakajima, Tetsuo× Tanaka, Kaoru× Hayata, Isamu× Ｇｕｉｌｌａｕｍｅ Ｖａｒｅｓ× 王 冰× 根井 充× 中島 徹夫× 田中 薫× 早田 勇 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Exposure of sublethal doses of ionizing radiation can induce protective mechanisms against a subsequent higher dose irradiation. This phenomenon, called radioadaptation (or adaptive response - AR), has been described in a wide range of biological models. In a series of studies, we demonstrated the existence of a radiation-induced AR in mice during late organogenesis. For better understanding of molecular mechanisms underlying AR in our model, we performed a global analysis of transcriptome regulations in cells collected from whole mouse fetuses. Using cDNA microarrays, we studied gene expression in these cells after in utero priming exposure to irradiation. Several combinations of radiation dose and dose-rate were applied to induce or not an AR in our system. Gene regulation was observed after exposure to priming radiation in each condition. Student's t-test was performed in order to identify genes whose expression modulation was specifically different in AR-inducing and non-AR-inducing conditions. Genes were ranked according to their ability in discriminating AR-specific modulations. Since AR genes were implicated in a variety of functions and cellular processes, we applied a functional classification algorithm, which clustered genes in a limited number of functionally related groups. We established that AR genes are significantly enriched for specific keywords. Our results show a significant modulation of genes implicated in signal transduction pathways. No AR-specific alteration of DNA repair could be observed. Nevertheless, it is likely that modulation of DNA repair activity results, at least partly, from post-transcriptional regulation. One major hypothesis is that deregulations of signal transduction pathways and apoptosis may be responsible for AR phenotype. In previous work, we demonstrated that radiation-induced AR in mice during organogenesis is related to Trp53 gene status and to the occurrence of radiation-induced apoptosis. Other work proposed that p53 may contribute to AR induction by shifting DSB end-joining activity from illegitimate error-prone rejoining to error-free direct ligation. For all these reasons, particular attention was given to the transcriptional behavior of p53-related genes in our model. Although average gene regulation fold was relatively small, a significant proportion of p53-related genes showed AR-specific modulation, indicating a role for directly and indirectly p53-related pathways in the induction of AR. Even though no evidence of specific DNA repair modulation at the transcriptional level was observed in adapted cells, a large amount of data suggested that induction of AR may result from modification of DNA repair activity. We studied H2AX kinetics following challenging irradiation in adapted and non-adapted cells. H2AX phosphorylation increased shortly after irradiation, and then decreased progressively during the subsequent 24 hours. No significant difference was observed between the rate of disappearance of H2AX in adapted and non-adapted cells, indicating that AR in this model seems not to be related with a modulation of DNA break rejoining speed. However, the peak of H2AX phosphorylation appeared slightly earlier in adapted than in non-adapted cells. In accordance with other data, these results are compatible with the hypothesis that the low adapting dose could induce a repair mechanism that, if activated at the time of challenging exposure with high doses of radiation, would lead to less residual damage. In conclusion, we observed transcriptional deregulations resulting from exposure to low dose X-rays. Our results highlighted some specific transcriptional response of cells when the characteristics of irradiation were efficient for inducing AR, indicating that AR may result from specific molecular mechanisms induced by exposure to priming dose of irradiation. To our knowledge and to date, this is the first report of AR-specific transcriptional deregulations in fetal mouse. |
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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 | The 6th Japan-France Workshop on Radiobiology and Isotopic Imaging | |||||
| 発表年月日 | ||||||
| 日付 | 2006-06-22 | |||||
| 日付タイプ | Issued | |||||
