Carcinogenesis, Vol. 20, No. 2, 243-248,
February 1999
© 1999 Oxford University Press
Characterization of cytochrome P450 expression in human oesophageal mucosa
1 Unit of Environmental Carcinogenesis and
2 Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France,
3 Division of Thoracic Surgery, University of Toronto, Ontario, Canada,
4 Imperial Cancer Research Fund, Molecular Pharmacology Unit, Biomedical Research Centre, Dundee, UK and
5 Molecular Epidemiology Unit, University of Leeds, Leeds LS2 9JT, UK
The expression of cytochrome (CYP) P450 enzymes in human oesophageal mucosa was investigated in a total of 25 histologically non-neoplastic surgical tissue specimens by using specific antibodies in immunoblots and by RT–PCR mRNA analysis. The presence of CYP1A, 2E1, 3A and 4A enzymes was demonstrated by both techniques; CYP2A reactive protein was also detected by immunoblot. The presence of CYP4B1 mRNA was established but no specific antibody was available for detection of the corresponding protein by immunoblot. CYP2B6/7 mRNA was not detected in any sample. The mRNA transcripts for CYP1A1, 2E1, 4A11 and 4B1 were consistently detected in the majority of samples (>84%), whereas CYP1A2 mRNA was only detected in 11 of 19 specimens examined. An RT–PCR method to differentiate CYP3A4 and 3A5 mRNA was developed. This demonstrated CYP3A5 mRNA expression in all samples tested, whereas CYP3A4 mRNA was not detectable, suggesting that CYP3A5 is the major CYP3A protein in human oesophagus. There were significant interindividual variations in the amount of proteins, ranging from 8-fold for CYP4A to 43-fold for CYP2E1. For each patient, data on exposure to risk factors for oesophageal cancer were available, including tobacco smoke, alcohol, gastro-oesophageal reflux and hot beverage consumption. None of these risk factors or other patient characteristics (age, sex, tumour location and tumour stage) were correlated with the protein level of the individual CYP enzymes as determined by quantitation of immunoblot staining. However, the small series of samples precludes any strong conclusion concerning the lack of such correlations. There were no differences between squamous cell carcinomas and adenocarcinomas in either the qualitative or quantitative expression of the CYP enzymes. These data demonstrate that a range of CYP enzymes are expressed in human oesophageal mucosa and indicate that this tissue has the capacity to activate chemical carcinogens to reactive DNA binding metabolites.
Abbreviations: CYP, cytochrome P450; NNO, N-nitrosamines.
6 Present address: Centre Francois Baclesse, CJF9603-EA1772, Caen, France
7 Present address: Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada
8 To whom correspondence should be addressed at Molecular Epidemiology Unit, School of Medicine, Algernon Firth Building, University of Leeds, Leeds LS2 9JT, UK Email: c.p.wild{at}leeds.ac.uk
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