Zhang Ting-Ting, Zhao Ge, Li Xiang, Xie Fu-Wei, Liu Hui-Min, Xie Jian-Ping
Key Laboratory of Tobacco Chemistry, Zhengzhou Tobacco Research Institute of CNTC , Zhengzhou , China.
Toxicol Mech Methods. 2015 Mar;25(3):212-22. doi: 10.3109/15376516.2015.1025345. Epub 2015 Mar 23.
2-Amino-9H-pyrido[2,3-b]indole (AαC), which is present in high quantities in cigarette smoke and also in fried food, has been reported to be a probable human carcinogen. However, few studies have reported on the genotoxicity and oxidative stress induced by AαC. This study investigated the genotoxic effects of AαC in human hepatoma G2 (HepG2) and human lung alveolar epithelial (A549) cells using the comet assay. Significant increases in DNA fragment migration indicated that AαC causes serious DNA damage in HepG2 and A549 cells. The role of oxidative stress in the mechanism of AαC-induced genotoxicity was clarified by measuring the level of intracellular reactive oxygen species (ROS), the GSH/GSSG ratio and the formation of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage. The results showed that the levels of ROS and 8-OHdG increased, whereas the GSH/GSSG ratio decreased. The concentration of 8-OHdG was positively related to DNA damage. Taken together, these results indicate that AαC can induce genotoxicity and oxidative stress and that AαC likely exerts genotoxicity in HepG2 and A549 cells through ROS-induced oxidative DNA damage. This is the first report to describe AαC-induced genotoxic and oxidative stress in HepG2 and A549 cells.
2-氨基-9H-吡啶并[2,3-b]吲哚（AαC）在香烟烟雾和油炸食品中含量很高，据报道它可能是一种人类致癌物。然而，很少有研究报道AαC诱导的遗传毒性和氧化应激。本研究使用彗星试验研究了AαC对人肝癌G2（HepG2）细胞和人肺泡上皮（A549）细胞的遗传毒性作用。DNA片段迁移的显著增加表明AαC在HepG2和A549细胞中引起严重的DNA损伤。通过测量细胞内活性氧（ROS）水平、谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值以及氧化DNA损伤标志物8-羟基脱氧鸟苷（8-OHdG）的形成，阐明了氧化应激在AαC诱导的遗传毒性机制中的作用。结果表明，ROS和8-OHdG水平升高，而GSH/GSSG比值降低。8-OHdG的浓度与DNA损伤呈正相关。综上所述，这些结果表明AαC可诱导遗传毒性和氧化应激，并且AαC可能通过ROS诱导的氧化DNA损伤在HepG2和A549细胞中发挥遗传毒性作用。这是首次报道AαC在HepG2和A549细胞中诱导的遗传毒性和氧化应激。
