Eicosapentaenoic Acid Alters Manganese Superoxide Dismutase Immunoreactive Protein Levels in Normal But not Maligant Central Nervous System Derived Cells

Abstract

The dose of radiation that safely can be administered to patients with malignant gliomas is limited by the potential for severe CNS morbidity. Manipulations that might increase the radiation sensitivity of gliomas and/or decrease injury to normal components of the CNS, e.g., the microvascular endothelium, one of the cell types believed to play a major role in radiation myelopathy, would provide a therapeutic benefit. One such approach may be the use of polyunsaturated fatty acids (PUFAs). PUFAs can inhibit tumor cell growth both in vitro ¹ and in vivo ². Moreover, Vartak et al.³, have recently shown that PUFAs are not only selectively cytotoxic to glioma cells, but also enhance the radiosensitivity of glioma cells. PUFAs have also been shown to reduce the severity of radiation-induced injury to normal tissue such as skin⁴ and CNS⁵. The damaging effects of ionizing radiation are due mainly to the generation of reactive oxygen species (ROS) which alter cell proteins, lipids and DNA. Therefore, we hypothesize that PUFAs may modify the response of cells to ionizing radiation by altering antioxidant enzymes that scavenge ROS. One such antioxidant enzyme, manganese Superoxide dismutase (Mn-SOD), a member of the Superoxide dismutase family of enzymes which scavenge Superoxide radicals, has been shown^6,7 to protect a variety of cells from ionizing radiation. In addition, several studies have shown^8,9 that PUFAs can alter Mn-SOD message, protein and activity. Therefore, we determined if one such PUFA, eicosapentaenoic acid (EPA; 20:5n-3), could alter Mn-SOD in a normal CNS-derived microvascular endothelial cell and a malignant CNS-derived glioma cell line.