title: Molecular changes in the esophageal epithelium after a subchronic exposure to cigarette smoke in the presence of bile-acid reflux.
abstract: BACKGROUND
  Gastroesophageal reflux of bile acids plays an important role in the development of Barrett's esophagus (BE)-associated esophageal adenocarcinoma (EAC). Cigarette smoke has been demonstrated to exacerbate the effects of reflux and thus the initial stages of EAC carcinogenesis. To date, no in vivo studies have been conducted to look at the concomitant effects of cigarette smoke and bile acids on EAC incidence.
  
  
  METHODS
  In this pilot study, rats that underwent esophagoduodenal anastomosis (EDA) surgery to induce reflux were exposed to whole-body cigarette smoke 3 weeks after surgery. Smoke exposure (135 mg/m³/day) was done for 4 h/day for 5 consecutive days and animals were euthanized after a 48-h recovery period.
  
  
  RESULTS
  Exposure to EDA-smoke accelerated the development of BE when compared to EDA-air. The presence of reflux caused a significant 3.5-fold increase in nuclear factor-κB-inducing kinase (NIK) staining (1.47 ± 0.6; p = 0.01). Animals with both reflux and smoking had the highest (10-fold; 4 ± 0.9) induction of cyclooxygenase-2 (COX-2) expression (p < 0.05). Similarly, there was a 10-fold increase in 4-aminobiphenyl (4-ABP) protein adducts identified in all smoke-exposed animals (p < 0.01).
  
  
  CONCLUSIONS
  Cigarette smoke aggravates reflux-induced BE and potentially accelerates the progression of BE to EAC through the loss of manganese superoxide dismutase (MnSOD), and overexpression of NF-κB- and COX-2-mediated factors.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
authors.forename: Harini S
authors.initials: HS
authors.lastname: Aiyer
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Nicholas
authors.initials: N
authors.lastname: Harper
authors.forename: Steven R
authors.initials: SR
authors.lastname: Myers
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D001655:Bile Reflux / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004386:Duodenum / Q000601:surgery; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004941:Esophagitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006454:Hemoglobins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D015415:Biomarkers; D051546:Cyclooxygenase 2; D006454:Hemoglobins; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D014028:Tobacco Smoke Pollution; D000097782:NF-kappaB-Inducing Kinase; C062091:hemoglobin, 4-aminobiphenyl-; C489691:Ptgs2 protein, rat