Mulder T P, Manni J J, Roelofs H M, Peters W H, Wiersma A
Department of Gastroenterology, University Hospital St Radboud, Nijmegen, The Netherlands.
Carcinogenesis. 1995 Mar;16(3):619-24. doi: 10.1093/carcin/16.3.619.
Glutathione S-transferase (GST) enzyme activity, GST isoenzyme composition and glutathione (GSH) concentration were assessed in normal and squamous cell carcinoma specimens of 14 patients with oral or oropharyngeal cancer and 11 patients with laryngeal cancer. Comparing malignant with normal oral/oropharyngeal tissues, no significant differences in GSH content, GST enzyme activity or isoenzyme composition were found. However, some tumours had up to 3-fold increased GST enzyme activities and 11 malignant samples over-expressed GST-pi. GST-pi was present in all normal and malignant oral/oropharyngeal specimens investigated, whereas class alpha and class mu were detected in only a few samples. GST-mu was present in 28% of the patients with oral/oropharyngeal tumors as compared with approximately 60% in the normal population. GST-alpha, -mu and -pi were detected in 91, 64 and 100% of the normal laryngeal tissues respectively. In laryngeal tumours significantly higher levels of GST-pi and GSH but significantly lower amounts of GST-alpha were detected. Levels of class mu GST were generally lower in cancerous tissues, but differences were not significant. In comparison with normal oral/oropharyngeal tissues, normal laryngeal tissues contained almost twice the amount of GST enzyme activity due to higher class alpha enzyme levels. It is concluded that GST-pi is elevated in 11 out of 14 tumours of the oral cavity and values are significantly increased in tumours of the larynx, which may contribute to the inherent anti-cancer drug resistance of these malignancies. In laryngeal tumours the increased GSH levels may confer additional resistance to radiation therapy.
对14例口腔或口咽癌患者以及11例喉癌患者的正常组织和鳞状细胞癌标本进行了谷胱甘肽S-转移酶（GST）酶活性、GST同工酶组成及谷胱甘肽（GSH）浓度的评估。将恶性组织与正常口腔/口咽组织进行比较，发现GSH含量、GST酶活性或同工酶组成无显著差异。然而，部分肿瘤的GST酶活性增加了3倍，11个恶性样本中GST-π过度表达。在所研究的所有正常及恶性口腔/口咽标本中均存在GST-π，而仅在少数样本中检测到α类和μ类同工酶。与正常人群中约60%的比例相比，28%的口腔/口咽肿瘤患者中存在GST-μ。正常喉组织中GST-α、-μ和-π的检测率分别为91%、64%和100%。在喉肿瘤中，检测到GST-π和GSH水平显著升高，但GST-α含量显著降低。癌组织中μ类GST水平通常较低，但差异不显著。与正常口腔/口咽组织相比，正常喉组织中GST酶活性几乎是其两倍，这是由于α类酶水平较高。研究得出结论，在14例口腔肿瘤中有11例GST-π升高，在喉肿瘤中其值显著增加，这可能导致这些恶性肿瘤固有的抗癌药物耐药性。在喉肿瘤中，GSH水平升高可能会增加对放射治疗的耐药性。
