Protection from radiation-induced alopecia with topical application of nitroxides: fractionated studies.
OBJECTIVE
Hair loss resulting from irradiation of the head and neck or from whole brain irradiation often leads to cosmetic, social, and psychological problems for the radiotherapy patient. Few successful clinical interventions are available. We have shown that nitroxides (stable free radicals) afford radiation protection against single-dose radiation-induced alopecia in a guinea pig model. Here we determine if topical nitroxide application provides protection from fractionated radiation treatment.


METHODS
Two symmetrical and contralateral areas (3 x 5 cm) of skin on the dorsal trunk of guinea pigs were shaved to a hair length of 0.25 cm. A 2 mL solution containing 70 mg/mL nitroxide (Tempo or Tempol) in 70% ethanol was topically applied to the skin surface of one side; 70% ethanol was applied to the contralateral (control) side 10 minutes before irradiation. Animals were placed in a special jig that held skin without decreasing blood flow to the treatment area and fractionated external beam radiation (7 Gy) was delivered daily for eight fractions over 10 days via a 4 MeV linear accelerator. Alopecia (hair density) was scored weekly for 13 to 14 weeks after radiotherapy, using a standardized reference with respect to hair loss and regrowth in the treatment field.


RESULTS
After radiation treatment, dry desquamation and gradual hair loss were observed for both control and nitroxide-treated skin; however, over weeks 4 to 11 postirradiation hair loss was much more pronounced in control animals when compared with nitroxide-treated animals. Hair density measurements for Tempol treatment over weeks 9 to 13 were approximately 75% compared with measurements in controls of approximately 25%. Tempo-treated animals exhibited hair density values of approximately 90% compared with 12% in controls over weeks 11 to 14. Tempol and Tempo treatments resulted in significant radioprotection. Histologic evaluation showed that radiation treatment alone in ethanol controls resulted in a marked decrease in the number of hair follicles and poor development of remaining follicles; however, nitroxide pretreatment resulted in no appreciable decrease in hair follicles and hair follicles appeared mature. This was also observed in unirradiated ethanol controls. Electron paramagnetic resonance studies revealed that topical nitroxide application did not result in measurable systemic concentrations of either drug.


CONCLUSIONS
The results of this study suggest that topical application of nitroxides may be useful in a clinical setting to reduce the undesirable toxicity of radiation-induced alopecia.
Cuscela
D
D
Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Coffin
D
D
Lupton
G P
GP
Cook
J A
JA
Krishna
M C
MC
Bonner
R F
RF
Mitchell
J B
JB
D000287:Administration, Topical; D000505:Alopecia / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006168:Guinea Pigs; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D017078:Laser-Doppler Flowmetry; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D013113:Spin Labels; C001803:tempol; C003959:TEMPO