Redox cycling of catechol estrogens generating apurinic/apyrimidinic sites and 8-oxo-deoxyguanosine via reactive oxygen species differentiates equine and human estrogens.
Redox cycling of catechol estrogens generating apurinic/apyrimidinic sites and 8-oxo-deoxyguanosine via reactive oxygen species differentiates equine and human estrogens.
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儿茶酚雌激素的氧化还原循环通过活性氧产生无嘌呤/无嘧啶位点和 8-氧代-脱氧鸟苷，从而区分马和人类雌激素。
DOI：
10.1021/tx1001282
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发表时间：
2010
影响因子：
4.1
通讯作者：
Bolton,JudyL
中科院分区：
文献类型：
--
作者：
Wang,Zhican;Chandrasena,EsalaR;Yuan,Yang;Peng,Kuan-wei;vanBreemen,RichardB;Thatcher,GregoryRJ;Bolton,JudyL
雌激素的代谢激活为儿茶酚，并进一步氧化为高活性邻苯二酚，造成DNA损伤，包括无嘌呤/脱嘧啶(AP)位点。4-羟基奎尼宁(4-OHEN)是雌激素替代制剂中存在的马雌激素的主要邻苯二酚代谢物，可引起DNA链断裂、氧化碱基以及稳定和净化的加合物。然而，4-OHEN直接形成AP位点的情况还没有得到表征。在本研究中，用醛反应探针法检测了4-OHEN和内源性邻苯二酚雌激素代谢物4-羟雌酮(4-OHE)体外诱导AP位点的作用。在氧化还原循环剂、铜离子和NADPH存在下，4-OHEN和4-OHE均能显著提高小牛胸腺DNA中AP位点的水平。B环不饱和邻苯二酚4-OHEN在不加铜的情况下诱导AP位点，而4-OHE需要铜。AP位点的产生也比4-OHEN快得多。对于两种儿茶酚雌激素，AP位点的水平与8-oxo-DG的水平呈线性相关，这意味着净化是由活性氧物种(ROS)而不是雌激素−DNA加合物的净化引起的。ROS调节剂，如清除过氧化氢的过氧化氢酶和铜(I)螯合剂，阻止了AP位点的形成。在MCF-7乳腺癌细胞中，加入NADH后，4-OHEN显著促进AP位点的形成。相反，在4-OHE处理的细胞中没有检测到明显的AP位点的诱导。马儿茶酚雌激素的较大氧化还原活性通过ROS产生快速氧化DNA损伤，氧化还原循环剂和有趣的是NADPH依赖的苯醌氧化还原酶增强了这一损伤。
Metabolic activation of estrogens to catechols and further oxidation to highly reactiveo-quinones generates DNA damage including apurinic/apyrimidinic (AP) sites. 4-Hydroxyequilenin (4-OHEN) is the major catechol metabolite of equine estrogens present in estrogen replacement formulations, known to cause DNA strand breaks, oxidized bases, and stable and depurinating adducts. However, the direct formation of AP sites by 4-OHEN has not been characterized. In the present study, the induction of AP sites in vitro by 4-OHEN and the endogenous catechol estrogen metabolite, 4-hydroxyestrone (4-OHE), was examined by an aldehyde reactive probe assay. Both 4-OHEN and 4-OHE can significantly enhance the levels of AP sites in calf thymus DNA in the presence of the redox cycling agents, copper ion and NADPH. The B-ring unsaturated catechol 4-OHEN induced AP sites without added copper, whereas 4-OHE required copper. AP sites were also generated much more rapidly by 4-OHEN. For both catechol estrogens, the levels of AP sites correlated linearly with 8-oxo-dG levels, implying that depuriniation resulted from reactive oxygen species (ROS) rather than depurination of estrogen−DNA adducts. ROS modulators such as catalase, which scavenges hydrogen peroxide and a Cu(I) chelator, blocked the formation of AP sites. In MCF-7 breast cancer cells, 4-OHEN significantly enhanced the formation of AP sites with added NADH. In contrast, no significant induction of AP sites was detected in 4-OHE-treated cells. The greater redox activity of the equine catechol estrogen produces rapid oxidative DNA damage via ROS, which is enhanced by redox cycling agents and interestingly by NADPH-dependent quinone oxidoreductase.
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影响因子：
3.8
作者：
V. Vogel;A. Yeomans;E. Higginbotham
通讯作者：
E. Higginbotham
影响因子：
4.1
作者：
S. Sarabia;B. Zhu;T. Kurosawa;M. Tohma;J. Liehr
通讯作者：
S. Sarabia;B. Zhu;T. Kurosawa;M. Tohma;J. Liehr
影响因子：
4.7
作者：
Lixin Shen;E. Pisha;Zhiwen Huang;Zishan Alam;R. Breemen;Judy L. Bolton
通讯作者：
Lixin Shen;E. Pisha;Zhiwen Huang;Zishan Alam;R. Breemen;Judy L. Bolton
开发用于分析人乳腺癌细胞中稳定的 4-羟基马萘醌-DNA 加合物的液相色谱电喷雾电离串联质谱方法。
影响因子：
4.1
作者：
Wang,Zhican;Edirisinghe,Praneeth;Sohn,Johann;Qin,Zhihui;Geacintov,NicholasE;Thatcher,GregoryRJ;Bolton,JudyL
通讯作者：
Bolton,JudyL
提高乳腺癌细胞中的 DNA 损伤阈值。
影响因子：
3.8
作者：
Mobley,JamesA;Brueggemeier,RobertW
通讯作者：
Brueggemeier,RobertW