Carcinogenesis Advance Access originally published online on January 30, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 25, No. 5, 723-727,
May 2004
Carcinogenesis vol.25 no.5 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Thioproline inhibits development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats
1 Department of Pathology and 2 Department of Dental and Oral Surgery, Shiga University of Medical Science, Seta-tsukinowa-cho, Ohtsu, Shiga 520-2192 and 3 Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa 920-8641, Japan
4 To whom correspondence should be addressed. Email: mukaisho{at}belle.shiga-med.ac.jp
Several epidemiological cohort studies have suggested that duodeno-gastroesophageal reflux per se induces Barrett's esophagus leading to increased risk of the development of esophageal adenocarcinoma (EAC). However, the exact causative factors behind EAC remain unclear. Recently, we designed a new duodenal contents reflux model which retained normal stomach function. In this model, duodenal contents flowed back into the esophagus and stomach resulting in repeated re-entry into the esophagus through the site of esophagojejunostomy. To elucidate the factors underlying the development of EAC, thiazolidine-4-carboxylic acid (thioproline, TPRO) was applied to the new reflux models as a nitrite scavenger and as a probe to detect reactive nitrogen species (RNS). Post-operatively, 31 animals were divided into two groups according to diet. Animals belonging to the control group were given normal diet (n = 18), while the TPRO group was given food containing 0.5% TPRO (n = 13). All esophageal sections in both groups were examined using hematoxylin and eosin staining and immunohistochemical analysis of inducible nitric oxide synthase (iNOS). EACs developed in 7 of 18 rats (38.9%) of the control group, whereas no EACs were detected in the TPRO group (Fisher's exact test, P < 0.05). Conversely, esophageal squamous cell carcinoma (ESCC) was detected in 1 of 18 rats (5.6%) of the control group and in 1 of 13 rats (7.7%) of the TPRO group. The incidence of ESCC was not significantly different between the two groups (P = 0.671). iNOS protein was overexpressed in Barrett's esophagus of both groups. The present results suggest that RNS such as nitric oxide and peroxynitrite and nitroso compounds derived from reflux of duodenal contents play an important role in the development of EAC, and that the primary causes of ESCC and EAC may differ.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. A. Abrams Review: Chemoprevention of esophageal adenocarcinoma Therapeutic Advances in Gastroenterology, July 1, 2008; 1(1): 7 - 18. [Abstract] [PDF]
|
|