Clustered gonocyte apoptosis in cultured fetal rat testes induced by accelerated heavy-ion-irradiations and its possible mechanisms
| Autor: | Bing, Wang, Tanaka, Kaoru, Shang, Yi, Fujita, Kazuko, Noda, Yuko, Doi, Kazutaka, Ninomiya, Yasuharu, Morimoto, Yasuko, Moreno, Stephanie.G, Herve, Coffigny, Hayata, Isamu, Murakami, Masahiro, Eguchi-Kasai, Kiyomi, Nenoi, Mitsuru |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Popis: | The increased clinical application of cancer radiotherapy and the human activities in space missions make the study on the biological effects from high-LET ionizing radiation a great concern for both public health and academic research. Investigations through the ground-based experiments using accelerated heavy ions are of critical importance to provide important scientific basis for radiation risk estimates and offer significant insight into the mechanisms regarding protection against radiation. In the previous France-Japan Workshop, we reported that heavy-ion irradiations on E15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male breeding activity in Wistar rats. To explore the possible mechanisms underlying radiation-induced clustered gonocyte apoptosis in fetal gonads, which played a vital role in the fate of postnatal testis development, carbon and neon-ion irradiations (neon ions, beam energy 400MeV/nucleon, LET 30keV/microm; carbon ions, beam energy 290MeV/nucleon, LET 13keV/microm) of cultured fetal rat testes were applied to investigations ever after focusing on cellular and molecular events with or without inhibitors (administered 2h prior to irradiations) of p53 (pifithrin-alpha;100microM), gap junction (lindane, 40microM), or pan-caspase (Z-VAD-FMK, 100microM), or nitric oxide specific scavenger (cPTIO, 200microM). Results showed that, in addition to the clustered distribution, the time course and the percentage of apoptosis on E15 equivalent in vitro appeared similar to that in utero in response to carbon and neon-ion irradiations. Further study using accelerated carbon-ion irradiations showed that irradiations induced increased p53 expression and decreased expressions of p21 and Bcl-2 in a dose dependent manner. The pan-caspase inhibitor effectively inhibited apoptosis occurrence and reduced the extent of clustered distribution, while such effects were not observed with the presence of p53 or gap junction inhibitor, or nitric oxide specific scavenger. These findings indicated that irradiations of cultured fetal testes manifested pathologically similar gonocyte apoptosis to that in utero. The apoptosis was independent on p53, gap junction and nitric oxide. p53 expression was possibly responsible for the response to radiation damage rather than induction of apoptosis. The syncytial organization of gonocytes played a key role in formation of the clustered apoptosis. The 7th Japan-France Workshop on Radiation Biology |
| Databáze: | OpenAIRE |
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