Short CommunicationDrug-Metabolizing Enzymes in Pharyngeal Mucosa and in Oropharyngeal Cancer Tissue
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.
References (19)
- et al.
Etiological and preventive aspects of human cancer
Prev Med
(1972) - et al.
Formation of mono- and diglucuronides and of other glycosides of benzo(a)pyrene-3,6-quinol by V79 cell-expressed human phenol UDP-glucuronosyltransferases of the UGT1 gene complex
Biochem Pharmacol
(1995) - et al.
Protein measurement with the Folin phenol reagent
J Biol Chem
(1951) - et al.
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Anal Biochem
(1987) - et al.
Tissue-specific 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible expression of human UDP-glucuronosyltransferase UGT1A6
Arch Biochem Biophys
(1996) - et al.
A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini
J Biol Chem
(1992) - et al.
The causes of cancerQuantitative estimates of avoidable risks of cancer in the United States today
J Natl Cancer Inst
(1981) - et al.
Effects of cigarette smoking and alcohol consumption in the aetiology of cancer of the oral cavity, pharynx and larynx
Int J Epidemiol
(1991) - et al.
Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among US veterans
Cancer
(1993)
Cited by (13)
UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term
2002, Biochemical PharmacologyCitation Excerpt :In contrast the UGT2 subfamily isoforms are encoded by distinct genes on chromosome 4 (each consisting of 6 exons) with each isoform having a different promoter sequence [6,7]. UGT isoforms are constitutively expressed in many tissues including liver, kidney, adipose, adrenal, lung, mammary gland, prostate and skin [8,9], jejunum, ileum, colon [10], pharyngeal mucosa and squamous cancer cells [11] as well as the brain [12]. The study of UGTs in extrahepatic tissues is important for several reasons.
AH receptor-controlled transcriptional regulation and function of rat and human UDP-glucuronosyltransferase isoforms
1998, Advances in Enzyme RegulationInhibition and induction of CYP enzymes in humans: an update
2020, Archives of ToxicologyIdentification of human UDP-glucuronosyltransferases involved in N-carbamoyl glucuronidation of lorcaserin
2012, Drug Metabolism and DispositionDrug metabolism by tumours: Its nature, relevance and therapeutic implications
2007, Expert Opinion on Drug Metabolism and Toxicology
- 1
Present address: Dr. D. Ullrich, Ostpassage 7, D-30853 Langenhagen, Germany.