title: Oxidative stress has a role in malignant transformation in Barrett's oesophagus.
abstract: Mechanisms underlying the development of oesophageal adenocarcinoma are poorly understood. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barrett's oesophagus, we measured myeloperoxidase activity, superoxide dismutase activity, glutathione content and total aromatic DNA adducts. Mucosal specimens came from 52 patients in 6 groups: symptomatic gastro-oesophageal reflux disease (GORD) without and with endoscopic oesophagitis, Barrett's epithelium without and with dysplasia, adenocarcinoma in the oesophagus and controls. In the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence, glutathione content was progressively lower and myeloperoxidase activity higher than in controls, plateauing at Barrett's epithelium without dysplasia. Only in Barrett's epithelium with dysplasia was SOD activity significantly increased. In all patient groups, DNA adduct levels were significantly higher than the control level. Though these levels between patient groups did not differ significantly, the level was highest in Barrett's epithelium without dysplasia and progressively lower in Barrett's with dysplasia and adenocarcinoma. Pooled data showed a negative correlation between glutathione content and DNA adducts (-0.28, p = 0.05). Simultaneous formation of DNA adducts, increased myeloperoxidase-related oxidative stress, decreased antioxidant capacity (glutathione content) and the negative correlation between glutathione content and DNA adducts in the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus indicate a role in the pathogenesis and malignant transformation related to oxidative stress.
authors.affiliation: Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Eero I T
authors.initials: EI
authors.lastname: Sihvo
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Salminen
authors.forename: Tuomo K
authors.initials: TK
authors.lastname: Rantanen
authors.forename: O Juhani
authors.initials: OJ
authors.lastname: Rämö
authors.forename: Markku
authors.initials: M
authors.lastname: Ahotupa
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
authors.forename: Merja I
authors.initials: MI
authors.lastname: Auvinen
authors.forename: Jarmo A
authors.initials: JA
authors.lastname: Salo
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology*; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000150:complications* / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis; D004938:Esophageal Neoplasms / Q000209:etiology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione