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Cytochrome P450 1B1 Expression in Rat Esophageal Tumorigenesis Promoted by Gastric and Duodenal Reflux

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Devlin, Andrea, Mcllroy, Marie, McKeen, Hayley D., Bonde, Pramode, Menezes, A. A. Carlos, Swarbrick, Christine J., Robson, Tracy, Hirst, David G., Campbell, F. Charles, McGuigan, James A. and McKeown, Stephanie (2009) Cytochrome P450 1B1 Expression in Rat Esophageal Tumorigenesis Promoted by Gastric and Duodenal Reflux. MOLECULAR CARCINOGENESIS, 48 (2). pp. 110-117. [Journal article]

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DOI: 10.1002/mc.20459

Abstract

Cytochrome P450 1B1 (CYP1B1) mRNA is constitutively expressed in most normal extra-hepatic tissues; however the protein is not detectable in these tissues but is expressed in a wide variety of tumors. CYP1B1 is responsible for the activation of a number of carcinogens present in tobacco smoke and food. A surgical model of rat esophageal tumorigenesis, promoted by gastric or duodenal reflux was used to determine CYP1B1 expression in premalignant esophageal tissue. Immunohistochemistry was performed using a modified amplified fluorescein tyramide protocol. CYP1B1 was not observed in normal esophageal mucosa, submucosa, or muscularis mucosa. Animals exposed to gastric reflux developed mild hyperplasia. Varying degrees of hyperplasia were observed in the duodenal reflux group. All regions of hyperplasia showed moderate or strong CYP181 immunoreactivity. Duodenal reflux induced a small number of premalignant changes: immunoreactivity was absent from the epithelium of squamous dysplasia (0/10), Barrett's esophagus (0/7), and majority of dysplastic Barrett's esophagus (1/4). Moderate or strong immunoreactivity was observed in the majority (7/8) of squamous cell carcinomas (SCCs) in situ. Immunoreactivity was also observed in the lamina propria and submucosa in association with inflammation, regardless of the severity of inflammation. The expression of CYP1B1 in hyperplasia, SCCs in situ, or in association with inflammation may increase the production of carcinogenic metabolites, which may promote esophageal tumorigenesis. (C) 2008 Wiley-Liss, Inc.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Molecular Medicine
Biomedical Sciences Research Institute > Pharmaceutical Science and Practice
Biomedical Sciences Research Institute > Molecular Medicine > Vascular Medicine
ID Code:4300
Deposited By:Professor Stephanie McKeown
Deposited On:05 Jan 2010 16:04
Last Modified:01 Jun 2011 16:49

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