title: DNA damage and S phase arrest induced by Ochratoxin A in human embryonic kidney cells (HEK 293).
abstract: Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, hepatotoxic and immunotoxic effects. The mechanisms underlying the nephrotoxicity of OTA remain obscure. To investigate DNA damage and the changes of the cell cycle distribution induced by OTA, human embryonic kidney cells (HEK 293 cells) were incubated with various concentrations of OTA for 24h in vitro. The results indicated that OTA treatment led to the production of reactive oxygen species (ROS) and to a decrease of the mitochondrial membrane potential (ΔΨm). OTA-induced DNA damage in HEK 293 cells was evidenced by DNA comet tails formation and increased expression of γ-H2AX. In addition, OTA could induce cell cycle arrest at the S phase in HEK 293 cells. The expression of key cell cycle regulatory factors that were critical to the S phase, including cyclin A2, cyclin E1, and CDK2, were further detected. The expression of cyclin A2, cyclin E1, and CDK2 were significantly decreased by OTA treatment at both the mRNA and protein levels. The apoptosis of HEK 293 cells after OTA treatment was observed using Hoechst 33342 staining. The results confirmed that OTA did induce apoptosis in HEK 293 cells. In conclusion, our results provided new insights into the molecular mechanisms by which OTA might promote nephrotoxicity.
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: The Supervision, Inspection & Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, PR China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: He
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China. Electronic address: xuwentaoboy@sina.com.
authors.forename: Wentao
authors.initials: W
authors.lastname: Xu
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Luo
authors.affiliation: The Supervision, Inspection & Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Supervision, Inspection & Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yingcong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006657:Histones / Q000096:biosynthesis; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009793:Ochratoxins / Q000494:pharmacology*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; D009793:Ochratoxins; C025589:ochratoxin A
keywords: Cell cycle arrest; DNA damage; HEK 293 cells; Ochratoxin A