Background: In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment leads to gastroesophageal reflux disease, multilayered epithelium (MLE, a presumed precursor in intestinal metaplasia), columnar-lined esophagus, dysplasia, and esophageal adenocarcinoma. Previously we have shown that columnar-lined esophagus in EGDA rats resembled human Barrett's esophagus (BE) in its morphology, mucin features and expression of differentiation markers (Lab. Invest. 2004;84:753-765). The purpose of this study was to compare the phenotype of rat MLE with human MLE, in order to gain insight into the nature of MLE and its potential role in the development of BE.

Tocopherols and tocotrienols, collectively known as vitamin E, are essential antioxidant nutrients. The biological fates and metabolite profiles of the different forms are not clearly understood. The objective of this study is to simultaneously analyze the metabolites of different tocopherols and tocotrienols in mouse and human samples. Using HPLC/electrochemical detection and mass spectrometry, 18 tocopherol-derived and 24 tocotrienol-derived side-chain degradation metabolites were identified in fecal samples. Short-chain degradation metabolites, in particular γ-and δ-carboxyethyl hydroxychromans (CEHCs) and carboxymethylbutyl hydroxychromans (CMBHCs) were detected in urine, serum and liver samples, with tocopherols additionally detected in serum and liver samples. The metabolite profiles of tocotrienols and tocopherols were similar, but new tocotrienol metabolites with double bonds were identified. This is the first comprehensive report describing simultaneous analysis of different side-chain metabolites of tocopherols and tocotrienols in mice and humans. Urinary metabolites may serve as useful biomarkers for nutritional assessment of vitamin E.

Background: Esophago-gastroduodenal anastomosis with rats mimics the development of human Barrett's esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed.

We previously demonstrated that oxidative stress subsequent to gastroesophageal reflux is an important driving force of esophageal adenocarcinoma (EAC) formation in the esophagogastroduodenal anastomosis (EGDA) rat model. This study investigated the possible tumor inhibitory effects of 2 antioxidants, a-tocopherol (389 and 778 ppm), N-acetylcysteine (NAC, 500 and 1,000 ppm), and their combination (389 and 500 ppm, respectively), as well as an antacid therapeutic agent, omeprazole (1,400 ppm). The rats were fed experimental diets 2 weeks after EGDA. All the animals were sacrificed 40 weeks after EGDA and the esophagi were harvested for histopathological examination. a-Tocopherol dosedependently decreased the incidence of EAC (p 5 0.03), with 778 ppm a-tocopherol reducing the incidence of EAC to 59% (16/27) in comparison with 84% (26/31) in the control group (p 5 0.04). Supplementation of a-tocopherol also increased the serum concentration of a-tocopherol. NAC at 500 and 1,000 ppm did not significantly decrease EAC incidence; however, the combination of a-tocopherol 389 ppm and NAC 500 ppm significantly reduced the incidence of EAC to 55% (15/27) (p 5 0.02). a-Tocopherol alone or in combination with NAC significantly reduced the number of infiltrating cells positively stained for 4-hydroxynonenal. Omeprazole showed only a slight nonsignificant inhibitory effect at the dose given. Our results suggest that supplementation with a-tocopherol inhibits the development of EAC in the rat EGDA model and similar inhibitory effect can be achieved when a lower dose of a-tocopherol is used in combination with NAC. ' 2008 Wiley-Liss, Inc.Key words: esophageal adenocarcinoma; inhibition; a-tocopherol; N-acetylcysteine; omeprazole In the last 30 years, the incidence of esophageal adenocarcinoma (EAC) in the United States has increased 4-fold, at a rate of 4-10% annually.1,2 Surgery remains the first choice in treatment, but even with improved techniques, the operative mortality rate is still around 10% and the 5-year survival rate is only 20-30%.3 It is, therefore, important to understand the etiology and pathogenesis of this disease and to develop strategies for its prevention.It is now clear that gastroesophageal reflux disease (GERD) and the formation of Barrett's esophagus (BE) are major risk factors for the development of EAC. Chronic GERD induces an adaptive metaplastic response in the squamous epithelium of the esophagus and transforms it into columnar epithelium marked by the appearance of glandular structures and goblet cells. 4,5 This type of pathological change is known as BE, and the risk of developing EAC in BE patients is 30 times higher than the general population. To mimic the pathological changes in human EAC, we developed a surgical procedure named esophagogastroduodenal anastomosis (EGDA), to produce gastroesophageal reflux and induce EAC in rats. 6 This model is superior to the previously used esophagoduodenal anastomosis model in that it maintains the stomach functions and relatively normal nutritional status...

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