Prior exposure to restraint stress enhances 7,12-dimethylbenz(a)anthracene (DMBA) induced DNA damage in rats

Over the years, several lines of evidence have emerged supporting the role of stress in the development and progression of cancer. Stress can cause an increase in the production of reactive oxygen species (ROS) and decrease in the in vivo antioxidant defense systems. A ROS-induced DNA damage in peripheral lymphocytes, liver and skin cells may be revealed by Comet assay. To test whether DNA is damaged by stress/DMBA/stress and DMBA, rats were exposed to multiple doses of DMBA in the presence and absence of restraint stress, and DNA damage was evaluated. Insignificant differences were detected in all the three cells tested (peripheral lymphocytes, liver and skin cells) between control and stress treatment in terms of frequencies of damaged DNA. The extent of DNA migration was enhanced in DMBA treated rats in a dose dependent manner. Pre-stress DMBA treatment showed still higher frequencies of damage in comparison with control, stress alone or DMBA alone groups. Thus, prior exposure to stress clearly enhanced the DMBA induced DNA damage, especially so in the skin cells (target organ of the carcinogen application) than liver and peripheral lymphocytes as observed on the basis of the extent of DNA migration (tail DNA) during single cell gel electrophoresis.