Objectives: Oral squamous cell carcinoma (oral SCC) comprises 90% of intraoral cancers, and is the seventh leading cancer in the United States. It has been well established that development of oral SCC correlates with carcinogen exposure resulting from the use of tobacco and ethanol products. While these clinical data strongly support the premise that the oral mucosa is an important site for extrahepatic carcinogen metabolism, little information exists on the distribution of carcinogen metabolizing enzymes, such as glutathione S-transferases (GSTs), within the oral cavity. The aim of this study was to determine enzymatic activity and intracellular localization of GSTs in normal, dysplastic, and malignant oral mucosa. Methods: Ten normal oral mucosal samples obtained from patients undergoing elective oral surgical procedures, fourteen samples of oral SCC tissue obtained from patients undergoing tumor resections at The Ohio State University and ten archival samples of formalin-fixed oral epithelial dysplasia were utilized. GST enzymatic activity was assessed in normal and SCC oral mucosal samples. Also, the immunohistochemical profiles of three GST isoforms {alpha, mu, and pi} were evaluated in normal, dysplastic, and SCC oral tissues. Results: Our results showed a trend towards increased GST functional activities in oral SCC tissues relative to normal mucosa. Using a Mann-Whitney rank sum test, the difference in GST functional activities between normal and oral SCC mucosa was not determined to be significant. Functional GST activities reflected heterogeneity among human donors. Immunohistochemical studies of all three GST isoforms demonstrated both increased expression and more uniform intraepithelial distribution in dysplastic and malignant mucosa as compared to normal oral tissue. Conclusion: Although functional GST activities appear to be higher in malignant oral mucosa, these data do not refute the possibility that GSTs exhibit a cytoprotective effect.
This work was supported by NIDCR grant PO1-DE12704 and in part, by NCI Grant 5P30CS16058.