title: Cytotoxicity of mequindox and its metabolites in HepG2 cells in vitro and murine hepatocytes in vivo.
abstract: Mequindox, a quinoxaline 1,4-dioxide, is widely used as a feed additive in the Chinese livestock industry because of its effective antibacterial properties. Many recent studies have found that mequindox is rapidly metabolized to numerous metabolites following administration to animals. There have, however, been few reports describing the cytotoxicity of mequindox metabolites. In this study, HepG2 cells were treated with mequindox (0, 2, 10, 50 or 100 μg/ml) or its major metabolites (0, 40, 100, 250 or 500 μg/ml) for 24h. Mice were administrated with mequindox (0, 50, 200 or 500 mg/kg.bw) for five days. DNA damage in the HepG2 cells and mouse hepatocytes was then assessed using an SCGE assay. The cell cycle of the HepG2 cells was also determined by flow cytometry. Mequindox was found to induce cell cycle arrest to the G2/M phase and cause dose-dependent DNA damage in HepG2 cells in vitro and in murine hepatocytes in vivo. Compared with mequindox, the major metabolites had much smaller effects on the cell cycle and caused much less DNA damage in HepG2 cells. And the results indicated that the process of metabolites formed by reduction of the MEQ acetyl group or reduction of the N → O groups could contribute to DNA damage in murine hepatocytes in vivo.
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. Electronic address: liuyingchun@shvri.ac.cn.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors.forename: Feiqun
authors.initials: F
authors.lastname: Xue
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. Electronic address: wangquan@shvri.ac.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D051379:Mice; D011810:Quinoxalines / Q000633:toxicity*
chemical_list: C545385:Mequindox; D011810:Quinoxalines
keywords: Cytotoxicity; HepG2 cell; Hepatocyte; Mequindox; Metabolite