Kinetics of Metallofullerenol Reactions with the Products of Water Radiolysis: Implications for Radiotherapeutics

Abstract

Radiotherapy is one of the basic treatments for cancer, involving the damage of cancer cells caused by reactive oxygen species generated upon ionizing radiation. As radiation and oxidative damage also affect normal cells, modern treatments include the application of effective radioprotectors in order to minimize side effects. In this study, pulse radiolysis was used for the kinetic evaluation of antiradical properties of three watersoluble metallofullerenols (MFs), Sc 3 N@C 80 (OH) 18 , Lu 3 N@ C 80 (OH) 18 , and Gd@C 82 (OH) 22 , as potential candidates for radioprotectors. The rate constants for their reactions with hydroxyl radicals (HO • ) are 2.24 × 10 9 , 4.32 × 10 9 , and 1.11 × 10 10 M −1 s −1 , respectively. The ability of MFs to trap HO • is well correlated with their protecting effect against hemolysis of human erythrocytes (red blood cells, RBC) induced by radiolysis under anaerobic conditions, suggesting that MFs effectively scavenge HO • radicals before they attack the biomembranes. This correlation is no longer valid for aerobic conditions, when HO • attacks the membrane lipids and the process turns into peroxidation mediated by lipidperoxyl radicals, but all three MFs exhibited much better radioprotection than vitamin C or Trolox (water-soluble analogue of tocopherol). The high polarity (bioavailability) of MFs and their ability to effectively trap radicals make them potential good inhibitors of oxidative damage caused as a side effect of radiotherapy.