Hydrated Electrons React with High Specificity with Cisplatin Bound to Single-Stranded DNA

被引:11
作者
Behmand, B. [1 ]
Cloutier, P. [1 ]
Girouard, S. [1 ]
Wagner, J. R. [1 ]
Sanche, L. [1 ]
Hunting, D. J. [1 ]
机构
[1] Univ Sherbrooke, Fac Med & Sci Sante, Grp Sci Radiat, Sherbrooke, PQ J1H 5N4, Canada
关键词
MAMMALIAN-CELLS; BREAKS; RADIOSENSITIZATION; RECOGNITION; MECHANISM; RADIATION; ATOMS; WATER;
D O I
10.1021/jp4089904
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Short oligonucleotides TTTTTGTGTTT and TTTTTTTGTTT in solution with and without cisplatin (cisPt) bound to the guanine bases were irradiated with gamma-rays at doses varying from 0 to 2500 Gy. To determine the effect of hydrated electrons from water radiolysis on the oligonudeotides, we quenched (OH)-O-center dot radicals with ethylenediaminetetraacetic acid (EDTA) and displaced oxygen, which reacts with hydrated electrons, by bubbling the solution with wet nitrogen. DNA strand breaks and platinum detachment were quantified by gel electrophoresis. Our results demonstrate that hydrated electrons react almost exclusively at the position of the cisPt adduct, where they induce cisPt detachment from one or both guanines in the oligonudeotide. Given the high yield of hydrated electrons in irradiated tissues, this reaction may be an important step in the mechanism of radiosensitization of DNA by cisPt
引用
收藏
页码:15994 / 15999
页数:6
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