Evaluation of tempol radioprotection in a murine tumor model

Free Radic Biol Med. 1997;22(7):1211-6. doi: 10.1016/s0891-5849(96)00556-4.

Abstract

Tempol, a stable nitroxide free radical compound, is an in vitro and in vivo radioprotector. Previous studies have shown that Tempol protects C3H mice against whole-body radiation-induced bone marrow failure. In this study, the radioprotection of tumor tissue was evaluated. RIF-1 tumor cells were implanted in female C3H mice 10 d prior to radiation. Groups of mice were injected intraperitoneally with Tempol (275 mg/kg) or PBS followed 10 min later by a single dose of radiation to the tumor bed. Tumor growth curves generated after 10 and 33.3 Gy doses of radiation showed no difference in growth between the Tempol- and PBS-treated animals. A full radiation dose-response experiment revealed a tumor control dose in 50% of the animals in 30 d (TCD(50/30)) value of 36.7 Gy for Tempol-treated mice and 41.8 Gy for saline-treated mice suggesting no protection of the RIF-1 tumor by Tempol. Tumor pharmacokinetics were done to determine why Tempol differentially protected bone marrow and not tumor cells. Differential reduction of Tempol in the RIF-1 tumor and bone marrow was evaluated with EPR spectroscopy 10, 20, and 30 min after injection. Bioreduction of Tempol to its corresponding hydroxylamine (which is not a radioprotector) occurred to a greater extent in RIF-1 tumor cells compared to bone marrow. We conclude that the differences in radioprotection may result from enhanced intratumor bioreduction of Tempol to its nonradioprotective hydroxylamine analogue. The nitroxides as a class of compounds may provide a means to exploit the redox differences between normal tissues and tumors.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / radiation effects
  • Cell Division / drug effects
  • Cyclic N-Oxides / metabolism
  • Cyclic N-Oxides / pharmacokinetics
  • Cyclic N-Oxides / pharmacology*
  • Electron Spin Resonance Spectroscopy
  • Female
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Transplantation
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology*
  • Neoplasms, Experimental / radiotherapy
  • Radiation Tolerance / drug effects*
  • Radiation-Protective Agents / pharmacokinetics
  • Radiation-Protective Agents / pharmacology*
  • Spin Labels

Substances

  • Cyclic N-Oxides
  • Radiation-Protective Agents
  • Spin Labels
  • tempol