Peter J. Giannini¹, Mark A. Morse², Christopher M. Weghorst^3,5, Ping Pei⁴ and Susan R. Mallery^4,5

¹Department of Oral Biology, University of Nebraska Medical Center College of Dentistry, Lincoln, Nebraska. ²Senior Toxicologist, Springborn Laboratories, Spencerville, Ohio. ³Division of Environmental Health Sciences, School of Public Health, The Ohio State University, College of Medicine, Columbus, Ohio. ⁴Department of Oral and Maxillofacial Surgery and Pathology, The Ohio State University, College of Dentistry, Columbus, Ohio. ⁵The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

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.