Ape1和碱基切除修复在HeLa细胞放射反应及热放射增敏中的作用
Role of Ape1 and base excision repair in the radioresponse and heat-radiosensitization of HeLa Cells.
作者信息
Batuello Christopher N, Kelley Mark R, Dynlacht Joseph R
机构信息
Indiana University, Department of Radiation Oncology, Indianapolis, Indiana 46202, USA.
出版信息
Anticancer Res. 2009 Apr;29(4):1319-25.
BACKGROUND
The mechanism by which heat sensitizes mammalian cells to ionizing radiation remains to be elucidated. We determined whether base excision repair (BER) is involved in heat-radiosensitization and report novel findings that provide insight regarding the role of BER in the radiation response of HeLa cells.
MATERIALS AND METHODS
An siRNA approach was utilized to suppress expression of AP endonuclease (Ape1), a critical enzyme of BER. Clonogenic survival curves were obtained for HeLa cells expressing normal or reduced Ape1 content and which had been irradiated, and these were compared to survival curves from cells that were irradiated prior to hyperthermia treatment.
RESULTS
The amount of heat-radiosensitization observed in Ape1-suppressed cells was similar to or slightly greater than that observed in cells expressing near-normal levels of Ape1. Interestingly, we also found that for unheated HeLa cells, suppressed expression of Ape1 resulted in enhanced resistance to X-rays.
CONCLUSION
The data suggest that Ape1, and therefore BER, is not involved in heat-radiosensitization. However, the observation that suppressed expression of Ape1 results in enhanced radioresistance supports the notion that BER may be detrimental to the survival of irradiated cells.
背景
热使哺乳动物细胞对电离辐射敏感的机制仍有待阐明。我们确定碱基切除修复（BER）是否参与热辐射增敏作用，并报告了一些新发现，这些发现为深入了解BER在HeLa细胞辐射反应中的作用提供了线索。
材料与方法
利用小干扰RNA（siRNA）方法抑制BER关键酶AP核酸内切酶（Ape1）的表达。获得了正常表达或Ape1含量降低且经照射的HeLa细胞的克隆存活曲线，并将其与热疗前照射的细胞的存活曲线进行比较。
结果
在Ape1抑制的细胞中观察到的热辐射增敏量与在Ape1表达接近正常水平的细胞中观察到的相似或略高。有趣的是，我们还发现，对于未加热的HeLa细胞，Ape1表达受抑制导致对X射线的抗性增强。
结论
数据表明Ape1，进而BER，不参与热辐射增敏作用。然而，Ape1表达受抑制导致辐射抗性增强这一观察结果支持了BER可能对受照射细胞的存活有害的观点。
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