Cleavage Enhancement of Specific Chemical Bonds in DNA by Cisplatin Radiosensitization

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• 作者：Fangxing Xiao ; Xinglan Luo ; Xianzhi Fu ; Yi Zheng
• 刊名：The Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：May 2, 2013
• 年：2013
• 卷：117
• 期：17
• 页码：4893-4900
• 全文大小：443K
• 年卷期：v.117,no.17(May 2, 2013)
• ISSN：1520-5207

文摘

X-ray photoelectron spectroscopy (XPS) is harnessed as an in situ efficient characterization technique for monitoring chemical bond transformation in DNA and cisplatin鈥揇NA complexes under synergic X-ray irradiation. By analyzing the variation of relative peak area of core elements of DNA as a function of irradiation time, we find that the most vulnerable scission sites in DNA are those containing phosphate and glycosidic bonds. Compared to DNA, the effective rate constants of the corresponding phosphodiester and glycosidic bond cleavages for cisplatin鈥揇NA complexes are 1.8 and 1.9 folds larger. These damages and their enhancements are similar to those induced by low energy electrons (LEE). Consistently, the magnitude of the secondary electron distribution produced by the X-rays on the cisplatin鈥揇NA complexes is considerably increased compared to that of pristine DNA. The data suggest that DNA radiosensization by cisplatin results not only from the sensitization of DNA to the action of LEE, but also from an increase the production of LEE at the site of binding of the cisplatin. The results provide new insights into the mechanisms of cisplatin-induced sensitization of DNA under X-ray irradiation, which could be helpful in the design of new cisplatin-based antitumor drugs.