title: Principal xenobiotic-metabolizing enzyme systems in human head and neck squamous cell carcinoma.
abstract: To better understand drug and carcinogen metabolism pathways in head and neck squamous cell carcinoma we assayed the principal drug- and carcinogen-metabolizing enzyme systems in both tumors and their corresponding adjacent non-tumoral tissues. Cytochromes P450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase and glutathione S-transferases (GST-alpha, GST-mu, GST-pi) were assayed by immunoblotting. GST activity, total glutathione, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase and sulfatase, were determined by spectral assays. Results showed the absence of all probed cytochromes P450 in tumors and non-tumoral tissues, including P450 1A1/1A2 known to be involved in tobacco-related carcinogenesis. No statistical difference was noted between tumors and adjacent non-tumoral tissues for most enzymes studied (GST-alpha, GST-mu, GST-pi, GST activity, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase and sulfatase). However, total glutathione concentrations were significantly higher (P < 0.05) in tumors (47 +/- 20 nmol/mg protein) than in non-tumoral tissues (19 +/- 9). On the contrary, epoxide hydrolase was significantly less expressed in tumors (18 +/- 9 micrograms/mg protein) compared to corresponding non-tumoral tissues (37 +/- 9). These data provide new information concerning human head and neck cancer biology that could possibly have clinical implications.
authors.affiliation: Head and Neck Surgery Department, Institut Gustave-Roussy, Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: Janot
authors.forename: L
authors.initials: L
authors.lastname: Massaad
authors.forename: V
authors.initials: V
authors.lastname: Ribrag
authors.forename: I
authors.initials: I
authors.lastname: de Waziers
authors.forename: P H
authors.initials: PH
authors.lastname: Beaune
authors.forename: B
authors.initials: B
authors.lastname: Luboinski
authors.forename: O
authors.initials: O
authors.lastname: Parise
authors.forename: A
authors.initials: A
authors.lastname: Gouyette
authors.forename: G G
authors.initials: GG
authors.lastname: Chabot
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009092:Mucous Membrane / Q000201:enzymology; D013429:Sulfatases / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015238:Sulfotransferases; D013429:Sulfatases; D004851:Epoxide Hydrolases; D005978:Glutathione