title: Controlled bile acid exposure to oesophageal mucosa causes up-regulation of nuclear γ-H2AX possibly via iNOS induction.
abstract: Using an in vitro model in which flatmounts of oesophagus was periodically exposed to bile acids, we demonstrate, using multiple methods, that the bile acid receptor TGR5, inducible nitric oxide synthase (iNOS) and γ-histone family 2A variant (γ-H2AX) are up-regulated. This indicates that bile acids cause up-regulation of iNOS, which further causes genotoxic stress as evidenced by increase of the highly sensitive marker, phosphorylated histone. In vitro nitric oxide (NO) assays showed increased production of nitric acid in the oesophageal epithelium exposed to the bile acids. This increase was inhibited in the presence of the nonspecific iNOS inhibitor aminoguanidine (AG). Cumulatively, the results of the present study provide suggestion that not only acid reflux, but also non-acid reflux of bile may cause genotoxic stress. These aspects merit to be tested in wide spectrum of Barrett epithelial tissues.
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China jiang8848@yeah.net.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China.
authors.forename: Shengqian
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The General Hospital of Jinan Military Command of PLA, Jinan, Shandong 250031, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China.
authors.forename: Yancheng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Gao
mesh_terms: D001471:Barrett Esophagus / Q000188:drug therapy / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D000071041:Esophageal Mucosa / Q000187:drug effects / Q000378:metabolism*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001647:Bile Acids and Salts; C473772:GPBAR1 protein, human; D006146:Guanidines; C468783:H2AX protein, human; D006657:Histones; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine
keywords: dysplasia; genotoxic stress; metaplasia; oesophageal adenocarcinoma; preneoplastic lesion