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2-[(氨丙基)氨基]乙硫醇(WR-1065)对V79细胞辐射诱导的DNA双链损伤及修复的影响。

The effect of 2-[(aminopropyl)amino] ethanethiol (WR-1065) on radiation induced DNA double strand damage and repair in V79 cells.

作者信息

Sigdestad C P, Treacy S H, Knapp L A, Grdina D J

出版信息

Br J Cancer. 1987 May;55(5):477-82. doi: 10.1038/bjc.1987.97.

Abstract

Radiation induced DNA double strand breaks are believed to be important lesions involved in processes related to cell killing, induction of chromosome aberrations and carcinogenesis. This paper reports the effects of the radioprotector 2-[(aminopropyl)amino]ethanethiol (WR-1065) on radiation-induced DNA damage and repair in V79 cells using the neutral elution method performed at pH 7.2 or pH 9.6. WR-1065 (4 mM) was added to the culture medium either 30 minutes prior to and during irradiation with Cobalt-60 gamma rays (for dose response experiments) or during the repair times tested (for DNA rejoining experiments). The results indicate that WR-1065 is an effective protector against the formation of radiation-induced double-strand breaks in DNA as measured using a neutral elution technique at either pH. The protector reduced the strand scission factors by 1.44 and 1.77 in experiments run at pH 9.6 and pH 7.2, respectively. The kinetics of DNA double-strand rejoining were dependent upon the pH at which the neutral elution procedure was performed. Unlike the results obtained with alkaline elution, rejoining of DNA breaks was unaffected by the presence of WR-1065 at either pH.

摘要

辐射诱导的DNA双链断裂被认为是与细胞杀伤、染色体畸变诱导和致癌作用相关过程中的重要损伤。本文报道了辐射防护剂2-[(氨丙基)氨基]乙硫醇(WR-1065)对V79细胞辐射诱导的DNA损伤和修复的影响,采用在pH 7.2或pH 9.6下进行的中性洗脱法。WR-1065(4 mM)在钴-60γ射线照射前30分钟及照射期间(用于剂量反应实验)或在测试的修复时间内(用于DNA重新连接实验)添加到培养基中。结果表明,WR-1065是一种有效的防护剂,可防止在任一pH值下使用中性洗脱技术测量的辐射诱导的DNA双链断裂的形成。在pH 9.6和pH 7.2进行的实验中,该防护剂分别将链断裂因子降低了1.44和1.77。DNA双链重新连接的动力学取决于进行中性洗脱程序的pH值。与碱性洗脱得到的结果不同,在任一pH值下,WR-1065的存在均不影响DNA断裂的重新连接。

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本文引用的文献

1
Protection against cis-dichlorodiammine Pt (II) cytotoxicity in vitro by cysteamine.
Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):585-8. doi: 10.1016/0360-3016(82)90689-7.
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Interaction of cultured mammalian cells with WR-2721 and its thiol, WR-1065: implications for mechanisms of radioprotection.
Int J Radiat Biol Relat Stud Phys Chem Med. 1983 May;43(5):517-27. doi: 10.1080/09553008314550611.
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Phase I clinical studies with WR-2721.
Cancer Clin Trials. 1980 Fall;3(3):217-21.
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The role of WR-2721 in radiotherapy and/or chemotherapy.
Cancer Clin Trials. 1980 Fall;3(3):211-6.
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A more general role for WR-2721 in cancer therapy.
Br J Cancer. 1980 May;41(5):832-4. doi: 10.1038/bjc.1980.150.

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