Radiosensitization of hypoxic tumor cells in vitro by nitric oxide
Radiosensitization of hypoxic tumor cells in vitro by nitric oxide
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DOI：
10.1016/s0360-3016(96)00329-x
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发表时间：
1996-09-01
影响因子：
7
通讯作者：
Song, CW
中科院分区：
文献类型：
--
作者：
Griffin, RJ;Makepeace, CM;Song, CW
目的：方法和材料：用NO供体2，2-二乙基-1-亚硝基肼钠盐（DEA/NO）和精胺/一氧化氮复合物（SPER/NO）将NO导入SCK肿瘤细胞悬液中，在pH7.4条件下，NO的半衰期分别为2.1 min和39 min。将细胞悬浮在含有DEA/NO或SPER/NO的培养基中，在缺氧或缺氧条件下进行不同时间的照射，并测定其集落形成能力。0.1、1.0和2.0mMDEA/NO的药物增强比（DER）分别为2.0、2.3和3.0，0.1、1.0和2.0mMSPER/NO的药物增强比（DER）分别为1.6、2.3和2.8。当DEA/NO和SPER/NO在溶液中孵育过夜以释放NO时，发现它们在低氧或有氧条件下没有放射增敏作用，表明NO供体的增敏是由于这些药物释放的NO分子。在较高浓度下，SPER/NO在有氧条件下有细胞毒性，而在缺氧条件下无细胞毒性，DEA/NO在有氧和缺氧条件下对细胞毒性均较弱.结论：NO供体DEA/NO和SPER/NO释放的NO在体外对乏氧细胞的放射增敏作用与氧一样有效，其在实体瘤乏氧细胞放射增敏中的应用有待进一步研究.版权所有（C）1996 Elsevier Science Inc.
Purpose: The effects of nitric oxide (NO) on the radiosensitivity of SCK tumor cells in oxic and hypoxic environments in vitro were studied.Methods and Materials: NO was delivered to cell suspensions using the NO donors 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), and a spermine/nitric oxide complex (SPER/NO), which release NO at half-lives of 2.1 min and 39 min at pH 7.4, respectively. The cells were suspended in media containing DEA/NO or SPER/NO for varying lengths of time under ode or hypoxic conditions, irradiated, and the clonogenicity determined.Results: Both compounds markedly radiosensitized the hypoxic cells. The drug enhancement ratios (DER) for 0.1, 1.0, and 2.0 mM DEA/NO were 2.0, 2.3 and 3.0, respectively, and those for 0.1, 1.0, and 2.0 mM SPER/NO were 1.6, 2.3, and 2.8, respectively, Aerobic cells were not radiosensitized by DEA/NO or SPER/NO, When DEA/NO and SPER/NO were incubated in solution overnight to allow release of NO, they were found to have no radiosensitizing effect under hypoxic or oxic conditions indicating the sensitization by the NO donors was due to the NO molecule released from these drugs, At the higher concentrations, SPER/NO was found to be cytotoxic in aerobic conditions but not in hypoxic conditions, DEA/NO was only slightly toxic to the cells in both aerobic and hypoxic conditions.Conclusions: NO released from NO donors DEA/NO and SPER/NO is as effective as oxygen to radiosensitize hypoxic cells in vitro, Its application to the radiosensitization of hypoxic cells in solid tumors remains to be investigated. Copyright (C) 1996 Elsevier Science Inc.