Elsevier

Biochemical Pharmacology

Volume 54, Issue 10, 15 November 1997, Pages 1159-1162
Biochemical Pharmacology

Short Communication
Drug-Metabolizing Enzymes in Pharyngeal Mucosa and in Oropharyngeal Cancer Tissue

https://doi.org/10.1016/S0006-2952(97)00347-XGet rights and content

Abstract

Cytochrome P4501A1 (CYP1A1) and the UDP-glucuronosyltransferase isoform UGT1A6 were studied in pharyngeal mucosa and squamous cancer tissue obtained from 27 male subjects (10 healthy nonsmoking volunteers, 10 smokers, and 7 smokers with pharyngeal cancer). CYP1A activity (7-ethoxyresorufin O-deethylase) was significantly induced in smokers as compared to nonsmokers (2.3 ± 1.1 and 0.8 ± 0.4 pmol · min−1 · mg protein−1, respectively). Immunoblot analysis demonstrated enhanced CYP1A1 protein in smokers. UGT activity towards 4-methylumbelliferone and 1-naphthol was also detectable in oropharyngeal mucosa. RT-PCR (reverse transcriptase-polymerase chain reaction) analysis indicated that UGT activity was at least in part due to the expression of UGT1A6. In cancer tissue, CYP1A activity was decreased in comparison with surrounding healthy mucosa (1.2 ± 0.9 in tumor tissue vs. 2.2 ± 0.7 pmol · min−1 · mg protein−1, respectively), whereas means and medians of UGT activity were unchanged. The results suggest that phase I and II drug-metabolizing enzymes are detectable in oropharyngeal mucosa and that CYP1A activity is inducible by constituents of cigarette smoke.

Section snippets

Subjects

Three groups of male subjects participated in the study: 10 smokers (smoking >20 cigarettes/day), 10 nonsmokers, and 7 tumor patients (smoking >20 cigarettes/day). The smokers, nonsmokers and tumor patients were 20 to 40 years old. No drugs and no additional diseases were known, and the patients’ alcohol consumption was moderate (<40 g/day). With smokers and nonsmokers biopsies were taken during tonsillectomy or nasal sinus surgery. Histological examination of the tumors revealed squamous cell

Results and Discussion

CYP1A activity was detectable in all pharyngeal tissue samples examined (Fig. 1). It was significantly increased in smokers despite large interindividual variations. As shown by immunoblot analysis, enhanced enzyme activity in smokers was due to increased CYP1A1 protein (Fig. 2A). Densitometry of pooled samples revealed that CYP1A1 was moderately induced ca. 1.5-fold (this trend was supported in individual samples from 3 smokers and 3 nonsmokers despite large variability; not shown). UGT

Acknowledgements

The authors wish to thank Prof. B. Beaune (INSERM U75, CHU Necker, Paris, France) for providing a CYP1A1 protein standard, Mrs. B. Kaltschmitt for her expert technical assistance, Mrs. B. Schulz, Mrs. A. v. Bank and Mrs. E. Schenk for typing the manuscript, and the Deutsche Forschungsgemeinschaft for financial support.

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Present address: Dr. D. Ullrich, Ostpassage 7, D-30853 Langenhagen, Germany.

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