The inhibitory effects of carbon monoxide (CO), generated by Ru(CO)3Cl-glycinate [CO-releasing molecule (CORM-3)], on developmental toxicity in zebrafish embryos induced by ionizing radiation with different linear energy transfer (LET) were studied. Zebrafish embryos at 5h post-fertilization were irradiated with X-ray (low-LET) and carbon-ion (high-LET) with or without pretreatment of CORM-3 1h before irradiation. CORM-3 pre-treatment showed a significant inhibitory effect on X-ray irradiation-induced developmental toxicity, but had little effect on carbon-ion irradiation-induced developmental toxicity. X-ray irradiation-induced significant increase in ROS levels and cell apoptosis could be modified by CORM-3 pretreatment. However, embryos exposed to carbon-ion irradiation showed significantly increase of cell apoptosis without obvious ROS generation, which could not be attenuated by CORM-3 pretreatment. CORM-3 could inhibit apoptosis induced by ionizing radiation with low-LET as an effective ROS scavenger. The expression of pro-apoptotic genes increased significantly after X-ray irradiation, but increased expression was reduced markedly when CORM-3 was applied before irradiation. Moreover, the protein levels of P53 and gamma-H2AX increased markedly after X-ray irradiation, which could be modified by the presence of CORM-3. The protective effect of CORM-3 on X-ray irradiation occurred mainly by suppressing ROS generation and DNA damage, and thus inhibiting the activation of P53 and the mitochondrial apoptotic pathway, leading to the attenuation of cell apoptosis and consequently alleviating X-ray irradiation-induced developmental toxicity at lethal and sub-lethal levels.

中文翻译：

---

Ru（CO）3Cl-甘氨酸盐对X射线和碳离子辐照在斑马鱼胚胎中诱导的发育毒性的影响。

Ru（CO）3Cl-甘氨酸盐[CO-释放分子（CORM-3）]产生的一氧化碳（CO）对不同线性能量转移（LET）的电离辐射诱导的斑马鱼胚胎发育毒性的抑制作用是研究过。在受精后5h，在辐照前1h用或不用CORM-3预处理的X射线（低LET）和碳离子（高LET）照射斑马鱼的胚胎。CORM-3预处理对X射线辐照引起的发育毒性具有明显的抑制作用，但对碳离子辐照引起的发育毒性几乎没有影响。X射线照射引起的ROS水平显着增加，并且细胞凋亡可以通过CORM-3预处理进行修饰。然而，暴露于碳离子辐照下的胚胎显示细胞凋亡显着增加，而没有明显的ROS产生，而CORM-3预处理不能减弱这些活性。CORM-3可以抑制以低LET作为有效ROS清除剂的电离辐射诱导的细胞凋亡。促凋亡基因的表达在X射线照射后显着增加，但是当照射前应用CORM-3时，表达的增加明显减少。此外，X射线照射后，P53和γ-H2AX的蛋白质水平显着增加，这可能因CORM-3的存在而改变。CORM-3对X射线辐射的保护作用主要是通过抑制ROS的产生和DNA损伤，从而抑制P53的激活和线粒体凋亡途径而发生的，