New directions for free radical cancer research and medical applications.
The nitroxides are stable, low molecular weight free radical compounds which are freely membrane permeable. These properties make the nitroxides valuable for the study of and possible protection against oxidative stresses. It is becoming increasingly clear that oxidative stress is important to the pathogenesis of cancer as well as to the development of treatments for cancer. Several nitroxides have been shown to interrupt the toxicity of oxidative stress with the protection against H2O2 toxicity and possibly ischemia/reperfusion injury being of primary importance. With respect to radiation, the nitroxides have afforded both in vitro and in vivo protection. The redox activity of the nitroxides may allow for the differential activity of these agents in normal versus tumor tissues. Further study of these compounds may yield a nitroxide with clinical applications as well as provide insight into the mechanisms of radiation cytotoxicity. Finally, the nitroxides have allowed us to explore the mechanisms of action of several chemotherapeutic agents. Understanding these processes is important to the process of ameliorating the toxicity of therapies and to the rationale design of future agents.
Hahn
S M
SM
Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Krishna
C M
CM
Mitchell
J B
JB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D013113:Spin Labels
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D011837:Radiation-Protective Agents; D013113:Spin Labels