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

Andrea Devlin, Marie Mcllroy, Hayley D. McKeen, Pramode Bonde, A. A. Carlos Menezes, Christine J. Swarbrick, Tracy Robson, David G. Hirst, F. Charles Campbell, James A. McGuigan, Stephanie McKeown

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    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.
    LanguageEnglish
    Pages110-117
    JournalMolecular Carcinogenesis
    Volume48
    Issue number2
    DOIs
    Publication statusPublished - Feb 2009

    Fingerprint

    Duodenogastric Reflux
    Cytochrome P-450 Enzyme System
    Stomach
    Carcinogenesis
    Hyperplasia
    Barrett Esophagus
    Carcinoma in Situ
    Inflammation
    Squamous Cell Carcinoma
    Mucous Membrane
    Anatomic Models
    Fluorescein
    Smoke
    Carcinogens
    Tobacco
    Epithelium
    Immunohistochemistry
    Food
    Messenger RNA
    Liver

    Cite this

    Devlin, A., Mcllroy, M., McKeen, H. D., Bonde, P., Menezes, A. A. C., Swarbrick, C. J., ... McKeown, S. (2009). Cytochrome P450 1B1 Expression in Rat Esophageal Tumorigenesis Promoted by Gastric and Duodenal Reflux. Molecular Carcinogenesis, 48(2), 110-117. https://doi.org/10.1002/mc.20459
    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. ; McKeown, Stephanie. / Cytochrome P450 1B1 Expression in Rat Esophageal Tumorigenesis Promoted by Gastric and Duodenal Reflux. In: Molecular Carcinogenesis. 2009 ; Vol. 48, No. 2. pp. 110-117.
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    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.",
    author = "Andrea Devlin and Marie Mcllroy and McKeen, {Hayley D.} and Pramode Bonde and Menezes, {A. A. Carlos} and Swarbrick, {Christine J.} and Tracy Robson and Hirst, {David G.} and Campbell, {F. Charles} and McGuigan, {James A.} and Stephanie McKeown",
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    Devlin, A, Mcllroy, M, McKeen, HD, Bonde, P, Menezes, AAC, Swarbrick, CJ, Robson, T, Hirst, DG, Campbell, FC, McGuigan, JA & McKeown, S 2009, 'Cytochrome P450 1B1 Expression in Rat Esophageal Tumorigenesis Promoted by Gastric and Duodenal Reflux', Molecular Carcinogenesis, vol. 48, no. 2, pp. 110-117. https://doi.org/10.1002/mc.20459

    Cytochrome P450 1B1 Expression in Rat Esophageal Tumorigenesis Promoted by Gastric and Duodenal Reflux. / 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.; McKeown, Stephanie.

    In: Molecular Carcinogenesis, Vol. 48, No. 2, 02.2009, p. 110-117.

    Research output: Contribution to journalArticle

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    AU - Bonde, Pramode

    AU - Menezes, A. A. Carlos

    AU - Swarbrick, Christine J.

    AU - Robson, Tracy

    AU - Hirst, David G.

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