title: Mequindox induced cellular DNA damage via generation of reactive oxygen species.
abstract: Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS.
authors.affiliation: College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Man
authors.initials: M
authors.lastname: Ouyang
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Peiqiang
authors.initials: P
authors.lastname: Mu
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Caihui
authors.initials: C
authors.lastname: Zhang
authors.forename: Weiying
authors.initials: W
authors.lastname: Xu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Michael S Y
authors.initials: MS
authors.lastname: Huen
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000822:Animal Husbandry; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D011810:Quinoxalines / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; C545385:Mequindox; D009153:Mutagens; D011810:Quinoxalines; D017382:Reactive Oxygen Species