Involvement of oxidative stress in experimentally induced reflux esophagitis and esophageal cancer.
OBJECTIVE
Recent studies have demonstrated that refluxed duodenal contents cause esophageal carcinoma in rats without exposure to carcinogens. Oxidative damage has long been related to carcinogenesis in human cancers and animal cancer models. The purpose here was to investigate the pathogenesis of esophageal cancer in the experiment of chronic duodenal content reflux without carcinogen.


METHODS
Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. In 10 rats the sham operation induced a midline laparotomy alone (Control). A total of 37 of 40 (92.5%) rats completed the study. In the EDA group, 27 (90%) rats completed the study. In the control group, 10 (100%) rats completely the study. They were sacrificed at the 35th week. Their esophagi were examined for the presence of cancer, Barrett's esophagus (BE), columnar line epithelium (CLE) and oxidative stress.


RESULTS
After 35 weeks of reflux, columnar dysplasia and squamous carcinoma were found. PCNA labeling index was higher in dysplastic and cancer tissue than that of normal. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barrett's esophagus, we measured Malondialdehyde (MDA), Superoxide dismutase (SOD) activity and Glutathione (GSH) content in EDA rats. Mucosal MDA levels were significantly increased in EDA groups compared with the normal controls. GSH and SOD levels were significantly decreased in EDA group compared with the normal control group.


CONCLUSIONS
We proposed that oxidative damage plays an important role in the formation of esophageal cancer with EDA model.
Inayama
Masato
M
Kinki University, Department of Surgery, 377-2 Ohno-Higashi Osaka Sayama, Osaka 589-8511, Japan.
Hashimoto
Naoki
N
Tokoro
Tadao
T
Shiozaki
Hitoshi
H
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000473:pathology; D004942:Esophagitis, Peptic / Q000150:complications* / Q000473:pathology; D005978:Glutathione / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood
D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione