title: DNA Damage in CD133-Positive Cells in Barrett's Esophagus and Esophageal Adenocarcinoma.
abstract: Barrett's esophagus (BE) caused by gastroesophageal reflux is a major risk factor of Barrett's esophageal adenocarcinoma (BEA), an inflammation-related cancer. Chronic inflammation and following tissue damage may activate progenitor cells under reactive oxygen/nitrogen species-rich environment. We previously reported the formation of oxidative/nitrative stress-mediated mutagenic DNA lesions, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine, in columnar epithelial cells of BE tissues and cancer cells of BEA tissues. We investigated the mechanisms of BEA development in relation to oxidative/nitrative DNA damage and stem cell hypothesis. We examined 8-nitroguanine and 8-oxodG formation and the expression of stem cell marker (CD133) in biopsy specimens of patients with BE and BEA by immunohistochemical analysis in comparison with those of normal subjects. CD133 was detected at apical surface of columnar epithelial cells of BE and BEA tissues, and the cytoplasm and cell membrane of cancer cells in BEA tissues. DNA lesions and CD133 were colocalized in columnar epithelial cells and cancer cells. Their relative staining intensities in these tissues were significantly higher than those in normal subjects. Our results suggest that BE columnar epithelial cells with CD133 expression in apical surface undergo inflammation-mediated DNA damage, and mutated cells acquire the property of cancer stem cells with cytoplasmic CD133 expression.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Raynoo
authors.initials: R
authors.lastname: Thanan
authors.affiliation: Faculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai 980-8574, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai 980-8574, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koike
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai 980-8574, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Mariko
authors.identifier: 0000-0003-3668-7214
authors.initials: M
authors.lastname: Murata
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan.
authors.forename: Shosuke
authors.identifier: 0000-0002-7525-7658
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000071916:AC133 Antigen / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D004947:Esophagus / Q000166:cytology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine