Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, United States.
Chem Res Toxicol. 2023 Jul 17;36(7):1002-1020. doi: 10.1021/acs.chemrestox.2c00235. Epub 2023 Jun 22.
Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature. Toward this end, we have studied the DNA interactions and photochemistry of -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride in the presence and absence of NaF, KF, NaCl, KCl, NaBr, KBr, NaI, and KI (350 nm hν, pH 7.0). Exposing pUC19 plasmid to UV light in solutions containing 400 mM KCl formed significantly more direct strand breaks in DNA compared to no-salt control reactions. In contrast, NaCl increased DNA damage moderately, while the sodium(I) and potassium(I) fluoride, bromide, and iodide salts generally inhibited cleavage (I > Br > F). A halide anion-induced heavy-atom effect was indicated by monitoring anthracene photodegradation and by employing the hydroxyl radical (OH) probe hydroxyphenyl fluorescein (HPF). These studies revealed that among no-salt controls and the eight halide salts, only NaCl and KCl enabled the anthracene to photosensitize the production of high levels of DNA-damaging reactive oxygen species (ROS). Pre-irradiation of -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride at 350 nm increased the amounts of chloride salt-induced OH detected by HPF in subsequent anthracene photoactivation experiments. Taking into consideration that OH and other highly reactive ROS are extremely short-lived, this result suggests that the pre-irradiation step might lead to the formation of oxidized anthracene photoproducts that are exceedingly redox-active. The fluorometric probes HPF and Singlet Oxygen Sensor Green revealed that KCl concentrations ranging from 150 to 400 mM and from 100 to 400 mM, respectively, enhanced -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride photosensitized OH and singlet oxygen (O) production over no-salt controls. Considering the relatively high levels of Na, K, and Cl ions that exist in the environment and in living organisms, our findings may be relevant to the phototoxic effects exhibited by anthracenes and other polycyclic hydrocarbons .
阐明多环芳烃光毒性的原因是理解这些化合物在自然界中有害影响的重要步骤。为此，我们研究了 -(9-蒽甲基)乙烷-1,2-二胺二盐酸盐在有和无 NaF、KF、NaCl、KCl、NaBr、KBr、NaI 和 KI 存在时的 DNA 相互作用和光化学反应（350nm hν，pH7.0）。将 pUC19 质粒暴露于含有 400mM KCl 的溶液中的紫外光下，与无盐对照反应相比，DNA 中形成的直接链断裂明显更多。相比之下，NaCl 适度增加 DNA 损伤，而氟化钠（I）、氟化钾（I）、溴化钠（I）和碘化钾（I）盐通常抑制裂解（I > Br > F）。通过监测蒽的光降解和使用羟基自由基（OH）探针羟基苯基荧光素（HPF），表明卤化物阴离子诱导的重原子效应。这些研究表明，在无盐对照和八种卤化物盐中，只有 NaCl 和 KCl 使蒽能够敏化产生高水平的 DNA 损伤活性氧物种（ROS）。在 350nm 处预先辐照 -(9-蒽甲基)乙烷-1,2-二胺二盐酸盐会增加随后蒽光活化实验中 HPF 检测到的氯化盐诱导的 OH 的量。考虑到 OH 和其他高反应性 ROS 极其短暂，这一结果表明预辐照步骤可能导致形成氧化的蒽光产物，这些产物具有极高的氧化还原活性。荧光探针 HPF 和单线态氧传感器绿表明，KCl 浓度范围为 150 至 400mM 和 100 至 400mM 分别增强了 -（9-蒽甲基）乙烷-1,2-二胺二盐酸盐敏化 OH 和单线态氧（O）的产生超过无盐对照。考虑到环境中和生物体中存在的相对较高水平的 Na、K 和 Cl 离子，我们的发现可能与蒽和其他多环碳氢化合物表现出的光毒性效应有关。
