Characterization of cytochrome P450 expression in human oesophageal mucosa

The expression of cytochrome (CYP) P450 enzymes in human oesophageal mucosa was investigated in a total of 25 histologically non-neoplastic surgical t issue specimens by using specific antibodies in immunoblots and by RT-PCR m RNA analysis. The presence of CYP1A, 2E1, 3A and 4A enzymes was demonstrate d by both techniques; CYP2A reactive protein was also detected by immunoblo t. 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, 2E 1, 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 dem onstrated CYP3A5 mRNA expression in all samples tested, whereas CYP3A4 mRNA was not detectable, suggesting that CYP3A5 is the major CYP3A protein in h uman oesophagus, There were significant interindividual variations in the a mount 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 char acteristics (age, sex, tumour location and tumour stage) were correlated wi th the protein level of the individual CYP enzymes as determined by quantit ation of immunoblot staining, However, the small series of samples preclude s any strong conclusion concerning the lack of such correlations. There wer e no differences between squamous cell carcinomas and adenocarcinomas in ei ther the qualitative or quantitative expression of the CYP enzymes. These d ata demonstrate that a range of CYP enzymes are expressed in human oesophag eal mucosa and indicate that this tissue has the capacity to activate chemi cal carcinogens to reactive DNA binding metabolites.