RESUMEN
The health-related effects of ionizing radiation on embryonic development and their underlying mechanisms are still unclear. The aim of this study was to investigate the role of Wnt signaling in mediating the developmental toxicity induced by heavy ion and proton radiation using zebrafish embryos. Zebrafish embryos were radiated with carbon ions or protons. HLY78, an activator of the Wnt signaling pathway, was added immediately after radiation. Carbon ion radiation induced a significant increase of mortality, and activating Wnt signaling using HLY78 after radiation significantly alleviated this stress. Both carbon ion and proton radiation significantly increased malformation rates and decreased hatching rates. Supplementation with HLY78 significantly reduced the effects induced by carbon ion radiation alone. After irradiation with carbon ions, embryos showed a significant decrease in heart rate, spontaneous movement, and locomotive behavior. The expression of apoptotic genes was significantly increased, while the expression of anti-apoptotic and Wnt-related genes was significantly decreased. Supplementation with HLY78 was able to reduce these effects. However, embryos irradiated with proton radiation did not show significant changes in the expression of Wnt-related genes. The results of this study improve our understanding of the mechanisms of carbon ion radiation-induced developmental toxicity, which potentially involves the inhibition of Wnt signaling.
Asunto(s)
Benzodioxoles/toxicidad , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/efectos de la radiación , Desarrollo Embrionario/efectos de los fármacos , Desarrollo Embrionario/efectos de la radiación , Fenantridinas/toxicidad , Radiación Ionizante , Pez Cebra/fisiología , Anomalías Inducidas por Medicamentos/patología , Anomalías Inducidas por Radiación/patología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/efectos de la radiación , Carbono , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de la radiación , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/efectos de la radiación , Iones , Actividad Motora/efectos de los fármacos , Actividad Motora/efectos de la radiación , Protones , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/efectos de la radiaciónRESUMEN
Studies have demonstrated that zebrafish are powerful tools for monitoring environmental toxicity, including radiation hazard. Here we investigated the developmental toxicity of ionizing radiation (IR) in an in vivo embryonic zebrafish model. The effects of heavy ion (12 C6+ ), proton, and X-ray radiation on early zebrafish embryos were determined. A similar dose-dependent decrease in the hatch and survival rate of zebrafish embryos was observed after exposure to these irradiations. Exposure of zebrafish embryos to 1-4 Gy IR caused significant loss of pigmentation. Quantitative real-time reverse transcription polymerase chain reaction, western blot analysis, and in situ hybridization (ISH) experiment revealed that atp5α1 was markedly upregulated in irradiated zebrafish embryos. In addition, IR resulted in a rapid decrease in total adenosine triphosphate (ATP) generation. With dual functions of synthesizing or hydrolyzing ATP, ATP synthase regulated H+ transport crossing the mitochondrial inner. Administration of the mitochondrial ATP synthase inhibitor, oligomycin, partially restored pigmentation in irradiated zebrafish embryos, but the ATPase inhibitor, BTB06584, had no effect. Taken together, these results showed that IR exposure downregulated zebrafish pigmentation through regulation of H+ ion transport in mitochondria.
Asunto(s)
Desarrollo Embrionario/efectos de la radiación , Pigmentación/efectos de la radiación , Exposición a la Radiación/efectos adversos , Pez Cebra/genética , Adenosina Trifosfatasas/antagonistas & inhibidores , Adenosina Trifosfatasas/genética , Animales , Clorobenzoatos/administración & dosificación , Daño del ADN/efectos de la radiación , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica/efectos de la radiación , Hibridación in Situ , ATPasas de Translocación de Protón Mitocondriales/antagonistas & inhibidores , ATPasas de Translocación de Protón Mitocondriales/genética , Oligomicinas/administración & dosificación , Pigmentación/genética , Radiación Ionizante , Sulfonas/administración & dosificación , Pez Cebra/crecimiento & desarrolloRESUMEN
Metal ion beams, which are used in surface modification of metals and alloys as ion beam micrometallurgy, are promising candidates for advanced applications in semiconductors and insulators. Doping with transition metal and rare-earth metal ions in semiconductors and insulators to form metallic nanoclusters attracted much more attention recently, since their applications in diluted magnetic semiconductors, electroluminescent devices, giant magnetic resistance, etc. In this paper, some experiments for metal ion beams will be presented, and various methods and technologies for the production of metal ion beams will be discussed.