Abstract 2909: Differences in cellular antioxidant activity in Burkitt's lymphoma and normal human lymphocytes.

Abstract

Abstract Cancer is a disease characterized by the uncontrolled growth of cells and invasion of these cells to other tissues. Less than 10% of all cancer mutations are caused by genetic factors while most mutations arise because of environmental factors. Environmental factors such as smoking, poor diet and obesity, alcohol, etc are known to trigger oxidative stress. Oxidative stress occurs when the concentration of reactive oxygen species (ROS) exceeds cellular antioxidant capacity. This in turn leads to oxidative damage and DNA mutations. Cells, however, have an antioxidant defense system that alleviates the effects of oxidative stress by preventing ROS from being formed or by stopping their damaging effects. A major part of this defense system is called the Antioxidant Response Element (ARE) which is located upstream of the promoter region of antioxidative and cytoprotective genes. The ARE is activated when oxidative stress occurs. Cells can also uptake antioxidants from their environment through passive and active transport when needed. The role of antioxidants is not to remove oxidants entirely, but to reduce them to sub-lethal levels within the cell. Diet plays an important role as a preventive measure against diseases caused by ROS. In this study we established a method to investigate the relationship between cell damage and nutrient uptake after exposing normal and cancer cells to a simulated oxidant environment (that induced ROS) and then to an antioxidant rich environment. We incubated Raji cells (Burkitt ’s lymphoma) and normal human lymphocytes with 20mM AAPH (2 2′-azobis(2-amidinopropane) dihydrochloride) and then exposed them to different known antioxidants namely, L-ascorbic acid, α-tocopherol, α-lipoic acid, glutathione, and resveratrol for 10, 20, 45, and 60 minutes. We analyzed the cell lysates or antioxidant activity after incubation with antioxidants using the oxygen radical absorbance capacity assay (ORAC) and measured for antioxidant activity. Results show that Raji cells have significantly higher antioxidant activity after exposed to an oxidant environment than when exposed to only an antioxidant environment(p-values > 0.05). On the other hand, normal human lymphocytes maintain relatively similar antioxidant activity when exposed to an oxidant followed by exposure an antioxidant environment, even when stimulated to undergo cell division (p-values <0.05). These results suggest that normal human lymphocytes are able to quench ROS quickly and are able to protect their DNA from damage and subsequent mutations, whereas Raji cells lack this mechanism and need to absorb more antioxidants from the environment, presumably because they are unable to produce enough antioxidants themselves. These results may help explain why cancer cells, which are usually depleted of antioxidants, are found to use antioxidants to protect themselves from chemotherapy drugs. Citation Format: Evita G. Weagel, Andres Martinez, Atif ElNaggar, Ping Guo Liu, Richard A. Robison, Kim L. O'Neill. Differences in cellular antioxidant activity in Burkitt's lymphoma and normal human lymphocytes. [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 2909. doi:10.1158/1538-7445.AM2013-2909