The effect of camphorquinone (CQ) and CQ-related photosensitizers on the generation of reactive oxygen species and the production of oxidative DNA damage
The effect of camphorquinone (CQ) and CQ-related photosensitizers on the generation of reactive oxygen species and the production of oxidative DNA damage
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DOI：
10.1016/j.biomaterials.2004.10.022
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发表时间：
2005-07-01
期刊：
影响因子：
14
通讯作者：
Geurtsen, W
中科院分区：
文献类型：
--
作者：
Pagoria, D;Lee, A;Geurtsen, W
最近的证据表明，在可见光（VL）照射后，CQ和CQ相关的光敏剂苯偶酰（BZ），二苯甲酮（BP），和9-芴酮（9-F）产生引发自由基，可以不加区别地与分子氧反应形成活性氧（ROS）。本研究的目的是确定VL辐照的CQ、BZ、BP和9-F是否由于在体外产生ROS而引起DNA损伤。研究了CQ和CQ相关光敏剂+/-二甲基-对甲苯胺（DMT）在无细胞体系中VL照射下的ROS形成。使用PhiX-174 RF 1超螺旋双链质粒DNA测定DNA损伤，并用4-（（9-吖啶羰基）氨基）-2，2，6，6-四甲基哌啶-1-氧基（克里思-9-AC）（一种荧光ROS敏感探针）定量ROS。VL辐照的CQ、BZ、BP和9-F（+/-DMT）在0.1、0.5和1.0 mM下以浓度依赖性方式产生显著的DNA损伤（p < 0.05）。克里思-9-AC显示，所有研究的VL照射的光敏剂产生了大量的ROS与BZ在DMT的存在下产生的最ROS后30，60和90分钟。VL照射CQ，BZ，BP和9-F +/- DMT继续产生大量的ROS后90分钟VL照射。因此，未来的研究应该评估VL辐照光敏剂在细胞中的作用以及抗氧化剂提供的可能保护作用。(C)2004爱思唯尔有限公司保留所有权利。
Recent evidence suggests that following visible-light (VL) irradiation, CQ and the CQ-related photosensitizers benzil (BZ), benzophenone (BP), and 9-fluorenone (9-F) generate initiating radicals that may indiscriminately react with molecular oxygen forming reactive oxygen species (ROS). The purpose of this investigation was to determine whether VL-irradiated CQ, BZ, BP, and 9-F cause DNA damage due to the generation of ROS in vitro. ROS formation by CQ and CQ-related photosensitizers +/- dimethyl-p-toluidine (DMT) was investigated in a cell-free system with VL irradiation. DNA damage was determined using PhiX-174 RF 1 supercoiled double-stranded plasmid DNA and ROS quantified with 4-((9-acridinecarbonyl)amino)-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO-9-AC), a fluorogenic ROS-sensitive probe. VL-irradiated CQ, BZ, BP, and 9-F (+/-DMT) produced significant DNA damage at 0.1, 0.5, and 1.0 mM and in a concentration-dependent manner (p < 0.05). TEMPO-9-AC revealed that all investigated VL-irradiated photosensitizers produced significant amounts of ROS with BZ in the presence of DMT generating the most ROS after 30, 60, and 90 min. VL-irradiated CQ, BZ, BP, and 9-F +/- DMT continued to generate significant amounts of ROS 90 min after VL irradiation. As a result, future investigations should evaluate the effect of VL-irradiated photosensitizers in cells and possible protective effects provided by antioxidants. (C) 2004 Elsevier Ltd. All rights reserved.