Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

Yang Yang; Liping Jiang; Yan She; Min Chen; Qiujuan Li; Guang Yang; Chengyan Geng; Liyun Tang; Laifu Zhong; Lijie Jiang; Xiaofang Liu

doi:10.1016/j.etap.2015.09.008

Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

Environ Toxicol Pharmacol. 2015 Nov;40(3):792-9. doi: 10.1016/j.etap.2015.09.008. Epub 2015 Sep 16.

Authors

Yang Yang¹, Liping Jiang², Yan She¹, Min Chen³, Qiujuan Li³, Guang Yang³, Chengyan Geng², Liyun Tang⁴, Laifu Zhong², Lijie Jiang⁵, Xiaofang Liu⁶

Affiliations

¹ 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.
² 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.
³ Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
⁴ Department of Gynaecology and Obstetrics, The Second Hospital of Dalian Medical University, No. 467 of Zhongshan Road, Dalian 116011, Liaoning, PR China.
⁵ Department of Internal Medicine, The Affiliated Zhong Shan Hospital of Dalian University, Dalian, Liaoning, PR China.
⁶ 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.

PMID: 26453893
DOI: 10.1016/j.etap.2015.09.008

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.

Keywords: DNA strand breaks; Lysosomal; Mitochondrial; Olaquindox; Oxidative stress.

MeSH terms

Cell Proliferation / drug effects
DNA / drug effects*
DNA Damage
Gene Expression Regulation / drug effects
HEK293 Cells
Humans
Lysosomes / drug effects*
Mitochondria / drug effects*
Quinoxalines / toxicity*
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects
Tumor Suppressor Protein p53 / metabolism*

Substances

Quinoxalines
Reactive Oxygen Species
TP53 protein, human
Tumor Suppressor Protein p53
DNA
olaquindox