Exogenous carbon monoxide protects the bystander Chinese hamster ovary cells in mixed coculture system after alpha-particle irradiation
Exogenous carbon monoxide protects the bystander Chinese hamster ovary cells in mixed coculture system after alpha-particle irradiation
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DOI：
10.1093/carcin/bgp301
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发表时间：
2010-02-01
期刊：
影响因子：
4.7
通讯作者：
Yu, K. N.
中科院分区：
文献类型：
--
作者：
Han, Wei;Wu, Lijun;Yu, K. N.
在混合共培养体系中，研究了CO释放分子CORM-2产生的一氧化碳（CO）对α粒子辐照后辐射诱导的旁效应（里贝）毒性的抑制作用。CO（CORM-2）处理对里贝诱导的p53结合蛋白1（BP 1）和微核（MN）的形成有明显的抑制作用，且呈浓度依赖性，但对直接照射的细胞群体中BP 1和MN的形成无明显的抑制作用。在此混合共培养系统中，通过使用NO合酶抑制剂或NADPH氧化酶特异性抑制剂处理，也证明了一氧化氮（NO）或超氧阴离子（O-2（中心点-））介导里贝的转导。通过氢化乙啶染色和荧光评估测量，在旁观者细胞中CO（CORM-2）处理减弱了升高的O-2（中心点-）。用外源性NO（NO2）或O-2（中心点-）（H2 O2）模拟NO/O-2介导的里贝，CO（CORM-2）处理也显示出对这些外源性因子毒性的保护作用。考虑到CO对里贝的抑制作用以及CO在疾病治疗中的广泛应用，低浓度的CO有望在放射治疗过程中保护正常组织免受里贝的损伤。
In the present work, the inhibitory effect of carbon monoxide (CO), generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on the toxicity of radiation-induced bystander effect (RIBE) after alpha-particle irradiation was studied in a mixed coculture system. CO (CORM-2) treatment showed a significant inhibitory effect to the formation of p53 binding protein 1 (BP1) and micronuclei (MN) induced by RIBE in a concentration-dependent manner, but in the directly irradiated cell population no distinct decreases of BP1 and MN formation were observed. In this mixed coculture system, nitric oxide (NO) or superoxide anion (O-2(center dot-)) was also proved to mediate the transduction of RIBE by using a NO synthase inhibitor or NADPH-oxidase-specific inhibitor treatment. The elevated O-2(center dot-) was attenuated by CO (CORM-2) treatment in the bystander cells as measured by hydroethidine staining and fluorescence assessment. The exogenous NO (sper) or O-2(center dot-) (H2O2) was used to mimic NO/O-2-mediated RIBE, and CO (CORM-2) treatment also showed a protective effect to cells against the toxicity of these exogenous factors. Considering the inhibitory effect of CO on RIBE and the wide use of CO in therapy of diseases, it is hoped that a low concentration of CO can protect normal tissues against RIBE during radiotherapy.