title: Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells.
abstract: Olaquindox (OLA) is a potent antibacterial agent used as a feed additive and growth promoter. In this study, the genotoxic potential of OLA was investigated in the human embryonic kidney cell line 293 (HEK293). Results showed that OLA caused significant increases of DNA migration. Lysosomal membrane permeability and mitochondrial membrane potential were reduced after treatment with OLA. OLA was shown to induce ROS production and GSH depletion. The expression of p53 protein is increased in cells incubated with OLA. The activation of p53 and ATM gene was assessed by exposure to OLA. Furthermore, NAC reduced DNA migration, ROS formation, GSH depletion and the expression of the p53 protein and gene. And desipramine significantly decreased AO fluorescence intensity and the expression of the p53 protein and gene. These results support the assumption that OLA exerted genotoxic effects and induced DNA strand breaks in HEK293 cells, possibly through lysosomal-mitochondrial pathway involving ROS production and p53 activation.
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: China-Japanese Joint Institute for Medical and Pharmaceutical Science, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: She
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Qiujuan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: China-Japanese Joint Institute for Medical and Pharmaceutical Science, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Geng
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Dalian Medical University, No. 467 of Zhongshan Road, Dalian 116011, Liaoning, PR China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Tang
authors.affiliation: China-Japanese Joint Institute for Medical and Pharmaceutical Science, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Laifu
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Internal Medicine, The Affiliated Zhong Shan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China. Electronic address: food@dlmedu.edu.cn.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Liu
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects*; D011810:Quinoxalines / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D011810:Quinoxalines; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004247:DNA; C013168:olaquindox
keywords: DNA strand breaks; Lysosomal; Mitochondrial; Olaquindox; Oxidative stress