OP088: Chronic restraint stress modifies global DNA methylation but not experimentally induced neoplastic lesions

Abstract

Purpose To determine if experimentally induced chronic stress modifies expression of microscopic neoplastic lesions, cell proliferation, oxidative cell damage and global DNA methylation in CF-1 mice tongues exposed to chemical carcinogenesis and controls. Methodology Experimental study. Fourteen male CF1 mice were treated with 4-Nitroquinoline 1-oxide (4NQO), as well as induction of chronic stress usingmovement restriction method. Fourteen similar specimens were treated only with 4NQO; 14 identical animals received only movement restriction and 14 others received no treatment. 4NQO was administered in drinking water during 16 weeks. Restraint stress treatment was administered in four 21 day cycles, 45 min long. All animals were sacrificed after 30 weeks. Blood samples were obtained to analyze amount of circulating corticosterone. Tissue samples were obtained to determine presence or absence of microscopic neoplastic lesions (Acantosis, Dysplasia, Carcinoma); severity of microscopic lesions (Differentiation Degree, Tumor Invasion Front); and immunohistochemical Ki67 and 8OHdG expression. Finally, percentages of global DNA methylation were determined. Software’s SPSS Statistics v19 and GraphpadPrism 5 were used for statistical analyses. Results Corticosterone levels (p = 0.042); microscopic neoplastic lesions (Acantosis, p = 0.001; Dysplasia, p = 0.001; Invasive Carcinoma, p = 0.005); cell proliferation (p = 0.001); oxidative cell damage (0.001) and global DNA methylation (p = 0.037) showed statistically significant differences among all groups. Differences were not statistically significant when only 4NQO-treated groups were analyzed. Conclusions Movement restriction induced chronic stress modifies corticosterone levels and global DNA methylation; however, it does not influence the development of experimentally induced neoplastic lesions.