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Sources of 2,5-diaminoimidazolone lesions in DNA damage initiated by hydroxyl radical attack.
Free Radical Research ( IF 3.6 ) Pub Date : 2020-09-01 , DOI: 10.1080/10715762.2020.1808632
Caroline Suzanne Thomas 1 , Hannah Catherine Pollard 1 , Yuriy Razskazovskiy 2 , Marina Roginskaya 1
Affiliation  

The present study reports radiation-chemical yields of 2.5-diaminoimidazolone (Iz) derivatives in X-irradiated phosphate-buffered solutions of guanosine and double-stranded DNA. Various gassing conditions (air, N20/O2 (4:1), N2O, vacuum) were employed to elucidate the contribution of several alternative pathways leading to Iz in reactions initiated by hydroxyl radical attack on guanine. In all systems, Iz was identified as the second by abundance guanine degradation product after 8-oxoguanine, formed in 1:5 (guanosine) and 1:3.3 (DNA) ratio to the latter in air-saturated solutions. Experimental data strongly suggest that the addition of molecular oxygen to the neutral guanine radical G(-H) plays a major in Iz production in oxygenated solutions of double-stranded DNA while in other systems it may compete with recombination of G(-H) with superoxide and/or alkyl peroxyl radicals. The production of Iz through hydroxyl radical attack on 8-oxoguanine was also shown to take place although the chemical yield of Iz (ca 6%) in this process is too low to compete with the other pathways. The linearity of Iz accumulation with dose also indicates a negligible contribution of this channel to its yield in all systems.



中文翻译:

羟自由基攻击引发的DNA损伤中2,5-二氨基咪唑啉酮损害的来源。

本研究报告了在鸟嘌呤和双链DNA的X射线磷酸盐缓冲溶液中2.5-二氨基咪唑酮(Iz)衍生物的放射化学产率。各种放气条件(空气,N 2 0 / O 2(4:1),N 2 O,真空)用于阐明由羟自由基攻击鸟嘌呤引发的反应中导致Iz的几种替代途径的贡献。在所有系统中,Iz被鉴定为仅次于8-氧鸟嘌呤的第二鸟嘌呤降解产物,其在空气饱和溶液中与后者的比例为1:5(鸟苷)和1:3.3(DNA)。实验数据强烈表明,将分子氧添加到中性鸟嘌呤基团G(-H)在双链DNA的含氧溶液中Iz的产生中起主要作用,而在其他系统中,它可能与G(-H)与超氧化物和/或烷基过氧自由基的重组竞争。尽管在该过程中Iz的化学收率(ca 6%)太低,无法与其他途径竞争,但通过羟基自由基攻击8-氧代鸟嘌呤也可产生Iz。Iz积累与剂量的线性关系还表明该通道在所有系统中对其产量的贡献可忽略不计。

更新日期:2020-09-21
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