诱变剂拦截剂叶绿酸对吖啶诱变剂ICR - 191与DNA相互作用及DNA损伤的减弱作用。
Attenuation of acridine mutagen ICR-191--DNA interactions and DNA damage by the mutagen interceptor chlorophyllin.
作者信息
Pietrzak Monika, Halicka H Dorota, Wieczorek Zbigniew, Wieczorek Jolanta, Darzynkiewicz Zbigniew
机构信息
Department of Physics and Biophysics, University of Warmia and Mazury in Olsztyn, Oczapowskiego 4, 10-719 Olsztyn, Poland.
出版信息
Biophys Chem. 2008 Jun;135(1-3):69-75. doi: 10.1016/j.bpc.2008.03.004. Epub 2008 Mar 30.
Abstract
We have investigated the ability of chlorophyllin (CHL) to interact with acridine mutagen ICR-191 (2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine) and also its ability to decrease binding of ICR-191 to DNA in a simple three-component competition system: CHL-ICR-DNA. Our data indicate a strong association of ICR-191 with CHL, stronger even than the association of ICR-191 with DNA. Calculations based on the measured affinity data show that a two- to three-fold excess of CHL reduces by about two-fold the concentration of the mutagen-DNA complex. We also exposed human leukemic HL-60 cells to ICR-191 in the absence and presence of CHL and measured the mutagen-induced DNA damage. The extent of DNA damage was assessed by analysis of histone H2AX phosphorylation. While ICR-191 induced significant increase in expression of phosphorylated H2AX (gammaH2AX), particularly in DNA replicating cells, this increase was totally abolished in the cells treated with ICR-191 in the presence of CHL.
摘要
我们研究了叶绿酸（CHL）与吖啶诱变剂ICR-191（2-甲氧基-6-氯-9-（3-（2-氯乙基）氨基丙基氨基）吖啶）相互作用的能力，以及在简单的三元竞争体系CHL-ICR-DNA中其降低ICR-191与DNA结合的能力。我们的数据表明ICR-191与CHL有很强的结合，甚至比ICR-191与DNA的结合更强。根据测得的亲和力数据进行的计算表明，CHL过量两到三倍可使诱变剂-DNA复合物的浓度降低约两倍。我们还在不存在和存在CHL的情况下，将人白血病HL-60细胞暴露于ICR-191，并测量诱变剂诱导的DNA损伤。通过分析组蛋白H2AX磷酸化来评估DNA损伤的程度。虽然ICR-191诱导磷酸化H2AX（γH2AX）的表达显著增加，尤其是在DNA复制细胞中，但在CHL存在下用ICR-191处理的细胞中，这种增加完全被消除。
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