Effects of sterigmatocystin on esophageal epithelium and experimental reflux esophagitis in rats.
Patients with reflux esophagitis experience an increased incidence of esophageal cancer. In China, this may be the result of contamination of the food supply by Aspergillus fungi, which is known to harbor sterigmatocystin, a carcinogenic mycotoxin. To delineate the potential link between sterigmatocystin and esophageal cancer, an experimental model of reflux esophagitis was developed in rats that had undergone a cardiectomy and partial pylorus ligation. The rats were treated with sterigmatocystin or saline, and esophageal squamous cell hyperplasia was assessed based on the pathological evaluation. The expression of proliferating cell nuclear antigen (PCNA), transporter associated with antigen processing 1 (TAP1) and low molecular weight protein 2 (LMP2) was determined by immunohistochemistry. Intraperitoneal administration of sterigmatocystin promoted the proliferation of squamous epithelium. In addition, it also increased the expression of PCNA in esophageal epithelial cells in rats with reflux esophagitis and was correlated with the increased severity of epithelial hyperplasia. The expression levels of TAP1 and LMP2, which are located in the cytoplasm of esophageal epithelial cells, were reduced in rats with reflux esophagitis, and sterigmatocystin exposure further decreased the expression. Thus, the downregulation of TAP1 and LMP2 proteins by sterigmatocystin may directly affect tumor immunity by allowing transformed cells to escape the host immune surveillance, thereby promoting esophageal cancer.
Department of Pathology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Pan-Zhuo
PZ
Tong
Guo-Jian
GJ
Zhang
Xiang-Hong
XH
Zhang
Xia
X
Yan
Jun-Ling
JL
Wang
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004942:Esophagitis, Peptic / Q000139:chemically induced / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013241:Sterigmatocystin / Q000633:toxicity*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D018809:Proliferating Cell Nuclear Antigen; C486172:Tap1 protein, rat; D013241:Sterigmatocystin; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases