Glutathione S-transferases and glutathione in human head and neck cancer

Abstract

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-π GST-πwas present in all normal and malignant oral/oropharyngeal specimens investigated, whereas class a and class μ were detected in only a few samples. GST-μ was present in 28% of the patients with oral/oropharyngeal tumours as compared with ∼60% in the normal population. GST-α, -μ and -π were detected in 91, 64 and 100% of the normal laryngeal tissues respectively. In laryngeal tumours significantly higher levels of GST-π and GSH but significantly lower amounts of GST-α were detected. Levels of class μ 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 α enzyme levels. It is concluded that GST-πis 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.