title: Investigation of quinocetone-induced mitochondrial damage and apoptosis in HepG2 cells and compared with its metabolites.
abstract: Quinocetone (QCT) has been widely used as an animal growth promoter in China. However, amounts of available data indicated that QCT probably had potential toxicity. The present study was aimed to investigate the genotoxicity, mitochondrial damage and apoptosis in HepG2 cells for QCT and its metabolites, DQCT and MQCA. QCT has seriously cytotoxic to HepG2 cells. The cell viability test and cytokinesis-block micronucleus test showed that the micronucleus frequency of cells treated with QCT has increased significantly, compared with DQCT and MQCA. With increasing of QCT concentrations, the genomic template stability and mitochondrial damage of HepG2 cells were aggravated. QCT-induced apoptosis in HepG2 cells were also observed. Data of caspase activities in measurement and real-time RT-PCR possibly suggested both of the mitochondria-dependent and mitochondria-independent pathways participated in the HepG2 cells apoptosis. However, all the results suggested that DQCT and MQCA showed only a little cytotoxic to HepG2 cells. In a word, QCT had toxic effects on HepG2 cells and resulted in the mitochondria-dependent and mitochondria-independent pathways of apoptosis, but the intermediate metabolites of QCT (DQCT and MQCA) were not.
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. Electronic address: z_cole@sina.com.
authors: Keyu
authors: K
authors: Zhang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Xiaoyang
authors: X
authors: Wang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Chunmei
authors: C
authors: Wang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Haihong
authors: H
authors: Zheng
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Tao
authors: T
authors: Li
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Sui
authors: S
authors: Xiao
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Mi
authors: M
authors: Wang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Chenzhong
authors: C
authors: Fei
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Lifang
authors: L
authors: Zhang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
authors: Feiqun
authors: F
authors: Xue
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D015162:Micronucleus Tests; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D010084:Oxidation-Reduction; D011810:Quinoxalines / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D011810:Quinoxalines; D012333:RNA, Messenger; C502851:quinocetone
keywords: 1,4-Bisdesoxyquinocetone; 3-Methylquinoxaline-2-carboxylic acid; Apoptosis; Genotoxicity; Mitochondrial damage; Quinocetone