Maintenance of Manganese Superoxide Dismutase (SOD2)- Mediated Delayed Radioprotection Induced by Repeated Administration of the Free Thiol Form of Amifostine

Abstract Murley, J. S., Nantajit, D., Baker, K. L., Kataoka, Y., Li, J. J. and Grdina, D. J. Maintenance of Manganese Superoxide Dismutase (SOD2)-Mediated Delayed Radioprotection Induced by Repeated Administration of the Free Thiol Form of Amifostine. Radiat. Res. 169, 495–505 (2008). Thiol-containing drugs such as WR1065, the free thiol form of amifostine, have been shown to induce a delayed radioprotective effect in both malignant and non-malignant cells. In mammalian cells exposed to a dose as low as 40 μM WR1065, the redox-sensitive nuclear transcription factor κB (NFκB) is activated, leading to an elevation in the expression of the antioxidant gene manganese superoxide dismutase (SOD2) and a concomitant increase in active SOD2 enzyme levels that peaks 24 to 32 h later. Exposure of cells to ionizing radiation during the period of elevated SOD2 enzymatic activity results in an enhanced radiation resistance. This is seen as an increase in surviving fraction as determined by standard colony formation ass...