Cuscela D, Coffin D, Lupton G P, Cook J A, Krishna M C, Bonner R F, Mitchell J B
Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer J Sci Am. 1996 Sep-Oct;2(5):273-8.
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.
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.
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.
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.
头颈部放疗或全脑放疗导致的脱发常常给放疗患者带来美观、社交和心理方面的问题。目前几乎没有成功的临床干预措施。我们已经证明，氮氧化物（稳定自由基）在豚鼠模型中能为单次辐射诱导的脱发提供辐射防护。在此，我们确定局部应用氮氧化物是否能为分次放射治疗提供防护。
将豚鼠背部躯干上两个对称且对侧的皮肤区域（3×5厘米）剃毛至毛发长度为0.25厘米。将一种2毫升的溶液（含70毫克/毫升氮氧化物（四甲基哌啶氧化物或4-羟基-TEMPO）于70%乙醇中）局部涂抹于一侧皮肤表面；在照射前10分钟，将70%乙醇涂抹于对侧（对照）皮肤。将动物置于一个特殊夹具中，该夹具可固定皮肤且不减少治疗区域的血流，通过一台4兆电子伏直线加速器，在10天内每天给予分次外照射（7戈瑞），共照射8次。放疗后13至14周内每周对脱发（毛发密度）进行评分，评分使用关于治疗区域内脱发和毛发生长的标准化参考标准。
放疗后，对照皮肤和经氮氧化物处理的皮肤均出现干性脱屑和逐渐脱发的情况；然而，在照射后第4至11周，对照动物的脱发情况比经氮氧化物处理的动物明显得多。在第9至13周，4-羟基-TEMPO处理组的毛发密度测量值约为对照组的75%，对照组约为25%。在第11至14周，四甲基哌啶氧化物处理组动物的毛发密度值约为90%，而对照组为12%。4-羟基-TEMPO和四甲基哌啶氧化物处理均产生了显著的辐射防护效果。组织学评估显示，仅乙醇对照组的放疗导致毛囊数量显著减少，剩余毛囊发育不良；然而，氮氧化物预处理并未导致毛囊数量明显减少，且毛囊看起来成熟。在未照射的乙醇对照组中也观察到了这一现象。电子顺磁共振研究表明，局部应用氮氧化物并未导致两种药物在体内可测量的全身浓度。
本研究结果表明，局部应用氮氧化物在临床环境中可能有助于降低辐射诱导脱发的不良毒性。
