Carcinogenesis, Vol 18, 2265-2270, Copyright © 1997 by Oxford University Press
SR Goldstein, GY Yang, SK Curtis, KR Reuhl, BC Liu, SS Mirvish, HL Newmark and CS Yang
In order to establish an animal model for studying the cause and prevention
of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's
esophagus (BE), factors affecting the pathogenic processes were
investigated in an esophagoduodenal anastomosis model with rats.
Experiments by us and others have shown that surgical treatment produced
reflux esophagitis with cell hyperproliferation, but not EAC. Additional
treatment with a carcinogen has been shown to be necessary for the
development of EAC, squamous cell carcinomas (SCC) or EAC/SCC mixtures. We
found that the surgically treated animals developed anemia due possibly to
reduced iron absorption. When the operated animals were supplemented with
iron, EAC occurred at a high rate (73%) after 30 weeks, and treatment with
N'-nitrosonornicotine did not enhance the rate of tumorigenesis. Treatment
with carcinogen, however, induced SCC in the group of rats killed after 22
weeks. The results suggest that iron overload, which is known to cause
oxidative damage, is an enhancing factor for adenocarcinogenesis. The
pathogenesis of EAC in the iron-supplemented, non-carcinogen treated group
resembles human esophageal adenocarcinogenesis in many features. All the BE
was the specialized type with goblet cells (containing sialomucin or
sulfomucin) and columnar cells (containing acid or neutral mucin) as well
as an incompletely developed brush border. Almost all of the BE was located
at the bottom of the esophagus and was continuous with the duodenal mucosa;
dysplasia became more frequent at later time points. All of the cancers
were well-differentiated mucinous EAC, and most of the EAC had an adjacent
area of BE with dysplasia. The results are consistent with the proposed
human sequence for pathogenic events of BE progression to 'BE with
dysplasia' and then to EAC. Esophagoduodenal anastomosis and iron treatment
in rats produces a high rate of BE and EAC which are morphologically
similar to human BE and EAC; this may be a useful animal model to study the
development and prevention of EAC in humans.
ARTICLES
Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, NJ 08855, USA.
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