Forrest Christopher R, O'Donovan David A, Yeung Ivan, Zeman Vlado, La Scala Giorgio, Neligan Peter C, Pang Cho Y
Division of Plastic Surgery, The Hospital for Sick Children Centre for Craniofacial Care and Research, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Plast Reconstr Surg. 2002 Apr 1;109(4):1311-23; discussion 1324. doi: 10.1097/00006534-200204010-00015.
It has been reported that radiotherapy-induced craniofacial deformities can occur in 66 to 100 percent of survivors of childhood head and neck cancers. Recent interest in the effectiveness of radioprotectors in the protection of normal tissue against radiation injury led us to investigate a possible role of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition. Therefore, the objective of this study was to use the radioprotective agent amifostine (Ethyol, WR-2721) as a probe to determine the effectiveness of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition after single-dose orthovoltage radiation to the infant rabbit orbital-zygomatic complex. Seven-week-old male New Zealand white rabbits were randomized into three groups (n = 10 each): group 1, 0 Gy (sham radiation); group 2, 35-Gy single-dose orthovoltage radiation; and group 3, 35-Gy single-dose orthovoltage radiation and amifostine (300 mg/kg intravenously, given 20 minutes before radiation). Serial radiographs and computed tomographic scans were obtained for cephalometric analysis, bone volume, and bone density measurements until skeletal maturity at 21 weeks. Significant (p < 0.05) reductions in orbital-zygomatic complex linear bone growth, bone volume, and bone density were observed after 35-Gy radiation compared with nonirradiated controls. No significant differences were noted between groups in cephalometric analysis of the nontreated (nonirradiated) left orbital-zygomatic complex, indicating no crossover effect from the radiation beam. However, pretreatment with amifostine, 20 minutes before 35-Gy radiation, resulted in significant (p < 0.05) preservation of linear bone growth, bone volume, and bone mineral density in the rabbit orbital-zygomatic complex compared with controls. This study demonstrated for the first time the effectiveness of a radioprotector in the prevention of radiation-induced craniofacial bone growth inhibition, and it paves the way for investigation into the pathogenic mechanism and prevention of radiotherapy-induced craniofacial deformities.
据报道，儿童头颈癌幸存者中66%至100%会出现放疗引起的颅面畸形。近期对辐射防护剂保护正常组织免受辐射损伤有效性的关注，促使我们研究辐射防护在预防辐射引起的颅面骨生长抑制方面的可能作用。因此，本研究的目的是使用辐射防护剂氨磷汀（Ethyol，WR-2721）作为探针，以确定在对幼兔眼眶颧复合体进行单剂量常压放疗后，辐射防护在预防辐射引起的颅面骨生长抑制方面的有效性。将7周龄雄性新西兰白兔随机分为三组（每组n = 10）：第1组，0 Gy（假照射）；第2组，35 Gy单剂量常压放疗；第3组，35 Gy单剂量常压放疗并给予氨磷汀（300 mg/kg静脉注射，在放疗前20分钟给予）。在21周骨骼成熟前，获取系列X线片和计算机断层扫描进行头影测量分析、骨体积和骨密度测量。与未照射的对照组相比，35 Gy放疗后眼眶颧复合体线性骨生长、骨体积和骨密度显著（p < 0.05）降低。在未处理（未照射）的左侧眼眶颧复合体的头影测量分析中，各组之间未观察到显著差异，表明无辐射束的交叉效应。然而，在35 Gy放疗前20分钟用氨磷汀预处理，与对照组相比，兔眼眶颧复合体的线性骨生长、骨体积和骨矿物质密度得到了显著（p < 0.05）的保留。本研究首次证明了辐射防护剂在预防辐射引起的颅面骨生长抑制方面的有效性，并为研究放疗引起的颅面畸形的发病机制和预防铺平了道路。
