Principal xenobiotic-metabolizing enzyme systems in human head and neck squamous cell carcinoma

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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-α, GST-μ, GST-π) were assayed by immunoblotting. GST activity, total glutathione, UDP-glucuronosyltransferase, β-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-α, GST-μ, GST-π, GST activity, UDP-glucuronosyltransferase, β-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 μg/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.

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