Janot F, Massaad L, Ribrag V, de Waziers I, Beaune P H, Luboinski B, Parise O, Gouyette A, Chabot G G
Head and Neck Surgery Department, Institut Gustave-Roussy, Villejuif, France.
Carcinogenesis. 1993 Jul;14(7):1279-83. doi: 10.1093/carcin/14.7.1279.
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.
为了更好地了解头颈部鳞状细胞癌中的药物和致癌物代谢途径，我们检测了肿瘤及其相应的相邻非肿瘤组织中主要的药物和致癌物代谢酶系统。通过免疫印迹法检测细胞色素P450（1A1/A2、2B1/B2、2C8 - 10、2E1、3A4）、环氧化物水解酶和谷胱甘肽S - 转移酶（GST -α、GST -μ、GST -π）。通过光谱分析测定GST活性、总谷胱甘肽、尿苷二磷酸葡萄糖醛酸基转移酶、β - 葡萄糖醛酸酶、磺基转移酶和硫酸酯酶。结果显示，在肿瘤组织和非肿瘤组织中，所有检测的细胞色素P450均不存在，包括已知参与烟草相关致癌作用的P450 1A1/1A2。在大多数研究的酶（GST -α、GST -μ、GST -π、GST活性、尿苷二磷酸葡萄糖醛酸基转移酶、β - 葡萄糖醛酸酶、磺基转移酶和硫酸酯酶）方面，肿瘤组织和相邻非肿瘤组织之间未发现统计学差异。然而，肿瘤组织中的总谷胱甘肽浓度（47±20 nmol/mg蛋白）显著高于非肿瘤组织（19±9）（P < 0.05）。相反，与相应的非肿瘤组织（37±9）相比，环氧化物水解酶在肿瘤组织中的表达明显较低（18±9 μg/mg蛋白）。这些数据提供了有关人类头颈部癌生物学的新信息，可能具有临床意义。
