An esophagogastroduodenal anastomosis model for esophageal adenocarcinogenesis in rats and enhancement by iron overload.
The aim of this study is to establish a good animal model for esophageal adenocarcinoma (EAC) and to test the hypothesis that iron over-nutrition enhances EAC formation. With rats, esophagogastroduodenal anastomosis (EGDA) was accomplished by anastomosing the duodenum to the gastroesophageal junction. Iron supplementation was given by i.p. injection of iron dextran (4 mg Fe/kg/week). This model mimics the development of human EAC by introducing mixed reflux of gastric and duodenal contents. At 40 weeks after surgery, the body weight, food intake, hemoglobin, total serum iron, transferrin saturation, serum albumin, and plasma levels of alpha-tocopherol, gamma-tocopherol and retinol of the EGDA rats were not significantly different from those of the non-operated controls. The animals generally had only mild esophagitis, except that the area surrounding the anastomosis opening had more severe esophagitis. Columnar-lined esophagus (CLE), CLE with dysplasia, and EAC were diagnosed in 53.5, 34.9 and 25.6%, respectively, of the 43 rats. Intraperitoneal iron supplementation significantly enhanced esophageal lesions with CLE, CLE with dysplasia, and EAC to 78.0, 53. 7 and 53.7%, respectively, of the 41 rats. All the tumors were well-differentiated mucinous adenocarcinomas at the squamocolumnar junction area, where most iron deposition was observed. EGDA avoids nutritional problems seen in other animal models for EAC. We believe that direct anastomosis of squamous epithelium to columnar epithelium and mixed reflux of gastric and duodenal contents lead to the formation of CLE and EAC. With this model, we demonstrated that iron supplementation significantly enhanced EAC formation, suggesting that iron over-nutrition could also be a risk factor for human EAC.
Chen
X
X
Laboratory for Cancer Research, College of Pharmacy and Laboratory for Animal Services, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Yang
G y
Gy
Ding
W Y
WY
Bondoc
F
F
Curtis
S K
SK
Yang
C S
CS
D002288:Adenocarcinoma, Mucinous / Q000209:etiology*; D000714:Anastomosis, Surgical; D000818:Animals; D001471:Barrett Esophagus / Q000150:complications; D003043:Cocarcinogenesis; D004195:Disease Models, Animal; D004386:Duodenum / Q000601:surgery; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000209:etiology*; D004947:Esophagus / Q000601:surgery; D005764:Gastroesophageal Reflux / Q000150:complications*; D005766:Gastrointestinal Contents; D007274:Injections, Intraperitoneal; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000150:complications*; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008679:Metaplasia; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000032:analysis; D013270:Stomach / Q000601:surgery; D014168:Transferrin / Q000032:analysis; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood
D012709:Serum Albumin; D014168:Transferrin; D014801:Vitamin A; D014810:Vitamin E; D007505:Iron-Dextran Complex; D007501:Iron