title: Effects of Ru(CO)3Cl-glycinate on the developmental toxicities induced by X-ray and carbon-ion irradiation in zebrafish embryos.
abstract: 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 γ-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.
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: School/Hospital of stomatology, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jing'e
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Si
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China. Electronic address: zhangh@impcas.ac.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School/Hospital of stomatology, Lanzhou University, Lanzhou 730000, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; Graduate School of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Yupei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; Graduate School of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; Graduate School of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Qianjing
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002244:Carbon / Q000009:adverse effects*; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000528:radiation effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000528:radiation effects; D020450:Heavy Ions / Q000009:adverse effects*; D009942:Organometallic Compounds / Q000494:pharmacology*; D011839:Radiation, Ionizing; D014965:X-Rays / Q000009:adverse effects*; D015027:Zebrafish
chemical_list: D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D002244:Carbon
keywords: Apoptosis; CORM-3; Carbon-ion irradiation; Oxidative stress; X-ray irradiation; Zebrafish embryos