Principal xenobiotic-metabolizing enzyme systems in human head and neck squamous cell carcinoma.
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.
Janot
F
F
Head and Neck Surgery Department, Institut Gustave-Roussy, Villejuif, France.
Massaad
L
L
Ribrag
V
V
de Waziers
I
I
Beaune
P H
PH
Luboinski
B
B
Parise
O
O
Gouyette
A
A
Chabot
G G
GG
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*
D007527:Isoenzymes; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015238:Sulfotransferases; D013429:Sulfatases; D004851:Epoxide Hydrolases; D005978:Glutathione