Epithelial cell hyperproliferation after biliopancreatic reflux into the esophagus of rats.
BACKGROUND
Chronic reflux of duodenal contents into the esophagus of rats produces severe esophagitis and exerts a co-carcinogenic effect on the proliferating cells by enhancing the formation of nitrosamine-induced esophageal carcinomas. We investigated the effect of the different components of the duodenal reflux on the epithelial cell proliferation of the lower esophagus.


METHODS
Sprague-Dawley rats underwent three surgical reflux models (biliopancreatic, pancreatic, and biliary) and a sham operation. Animals were sacrificed at 72 hours, 6 weeks, and 9 weeks after the operation. Histology and cell proliferation, determined by ornithine decarboxylase activity, polyamine (putrescine, spermidine, spermine) levels, and proliferating cell nuclear antigen labeling index of the basal and suprabasal layers, were studied in the distal esophagus.


RESULTS
Both biliopancreatic and pancreatic reflux induced severe esophagitis starting on week 6. Suprabasal proliferating cell nuclear antigen labeling index significantly increased throughout the 9 weeks of the study in the biliopancreatic and pancreatic reflux groups, although this increase was earlier in the former group. Ornithine decarboxylase activity and polyamine levels were significantly increased in the biliopancreatic and pancreatic groups on week 6, decreasing on week 9.


CONCLUSIONS
Increased esophageal cell proliferation after both biliopancreatic and pancreatic reflux into the lower esophagus may therefore be one mechanism by which duodenal-content reflux stimulates esophageal carcinogenesis in experimental animals.
Pera
M
M
Department of Surgery, Hospital Clinic i Provincial, University of Barcelona Medical School, Spain. pera@medicina.ub.es
Grande
L
L
Gelabert
M
M
Figueras
X
X
Pera
M
M
Palacín
A
A
Elena
M
M
Cardesa
A
A
Tiburcio
A F
AF
Trastek
V F
VF
D000818:Animals; D001655:Bile Reflux / Q000473:pathology*; D015317:Biogenic Polyamines / Q000032:analysis; D002455:Cell Division; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000209:etiology; D004942:Esophagitis, Peptic / Q000209:etiology; D004947:Esophagus / Q000473:pathology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000032:analysis; D010182:Pancreatic Diseases / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D015317:Biogenic Polyamines; D018809:Proliferating Cell Nuclear Antigen; D009955:Ornithine Decarboxylase