Functional activities and immunohistochemical cellular distribution of glutathione s-transferases in normal, dysplastic, and squamous cell carcinoma human oral tissues

Abstract

Clinical data show a strong correlation between tobacco and alcohol use and the development of oral squamous cell carcinoma (SCC). While this association implies that the oral mucosa actively metabolizes carcinogens, there is little information which depicts the carcinogen metabolizing enzymes within the oral cavity. Glutathione S-transferases (GSTs) primary function is to detoxify carcinogens by increasing their water solubility, GSTs represent key carcinogen metabolizing enzymes. Notably, individuals with a null phenotype for certain GST isoforms are at an increased risk to develop cancer. This study investigated the function and distribution of GSTs in human oral tissues. Our results from this pilot study showed a trend towards higher GST activities in SCC tissues relative to normal mucosa. Also, relative to normal tissues, the SCC and epithelial dysplasia samples showed a more intense and uniform GST intracellular distribution. GST activities are increased in many high grade cancers. Similarly, our data suggest that GST upregulation occurs in at least a subset of precancerous and malignant oral lesions.

Keywords: carcinogen metabolism; dysplasia; glutathione transferases; oral squamous cell carcinoma.

Figure 1

Western blot analysis for GST A1-1, M2-2, and P1-1 demonstrating GST antibody specificity.

Figure 2

GST A1-1 expression in normal oral mucosa (100X). Mild GST expression is primarily localized to the cytoplasm of cells within the basal layer.

Figure 3

GST P1-1 expression in dysplastic oral mucosa (100X). Moderate GST expression is demonstrated throughout the entire epithelium.

Figure 4

GST P1-1 expression in well-differentiated oral SCC (40X). Moderate GST expression is observed to be more intense within the basal cells of the invading epithelial islands.