Abstract 3546: S-Glutathionylation of buccal mucosal cell proteins as biomarkers of oxidative stress.

Abstract

Abstract Many anticancer drugs produce reactive oxygen species (ROS) that directly or indirectly lead to toxicities. As a conduit to drug development we have identified S-glutathionylated (post-translational addition of glutathione to susceptible cysteine residues) serine proteinase inhibitors (serpin's A1 and A3) as plausible biomarkers for drug exposure in both rodent and human blood. Commercial mouthwashes often contain redox-altering agents such as hydrogen peroxide (H2O2) and/or ethanol. Oxidative damage in buccal mucosa cells is associated with etiology of oral cancers and we hypothesized that these cells may also serve to provide a surrogate tissue source for biomarker analysis to measure S-glutathionylated proteins. Using an approved clinical protocol for exfoliated buccal cell samples, we have identified a number of S-glutathionylated proteins, including actin, in samples from volunteers following standard treatments with a commercial mouthwash containing H2O2 (1.5%). Their identities are similar to those discovered using in vitro experiments with the human buccal cell line TR146. Our current data show a time and dose-dependent increase in S-glutathionylation of buccal cell sample profiles in normal volunteers following four days of exposure dosing to H2O2 containing mouthwash. Increases in protein S-glutathionylation occurred immediately following exposure and remained for 30min following treatments. Higher levels of S-glutathionylation were maintained with each subsequent daily exposure. These increased levels of S-glutathionylation preceded the transcriptional activation of ROS sensitive genes, incuding ATF3. The identification of biomarkers that evaluate the effects of oxidative stress in the oral cavity may define at-risk populations for oral cancer and may be useful as direct biomarkers for the impact of drugs on general redox status. Citation Format: Christina L. Grek, Yefim Manevich, Danyelle M. Townsend, Kenneth D. Tew. S-Glutathionylation of buccal mucosal cell proteins as biomarkers of oxidative stress. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3546. doi:10.1158/1538-7445.AM2013-3546