title: Genotoxic and oxidative stress effects of 2-amino-9H-pyrido[2,3-b]indole in human hepatoma G2 (HepG2) and human lung alveolar epithelial (A549) cells.
abstract: 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.
authors: Key Laboratory of Tobacco Chemistry, Zhengzhou Tobacco Research Institute of CNTC , Zhengzhou , China.
authors: Ting-Ting
authors: TT
authors: Zhang
authors: Ge
authors: G
authors: Zhao
authors: Xiang
authors: X
authors: Li
authors: Fu-Wei
authors: FW
authors: Xie
authors: Hui-Min
authors: HM
authors: Liu
authors: Jian-Ping
authors: JP
authors: Xie
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000378:metabolism; D002243:Carbolines / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D009994:Osmolar Concentration; D016877:Oxidants / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002243:Carbolines; D009153:Mutagens; D016877:Oxidants; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione; C017822:2-amino-9H-pyrido(2,3-b)indole
keywords: 2-amino-9H-pyrido[2,3-b]indole (AαC); A549 cells; HepG2 cells; genotoxic effects; oxidative stress