Kuechler Alma, Dreidax Mareike, Pigorsch Steffi U, Liehr Thomas, Claussen Uwe, Wendt Thomas G, Dunst Jürgen
Department of Radiation Oncology, Friedrich Schiller University, Jena, Germany.
Strahlenther Onkol. 2003 Jul;179(7):493-8. doi: 10.1007/s00066-003-1095-z.
Amifostine is a radioprotective drug applied to reduce acute radiation toxicity during a course of conventionally fractionated radiotherapy. In the present study, amifostine was used in patients undergoing adjuvant radiochemotherapy for rectal cancer. It was described previously that additional application of amifostine led to less acute skin and bowel toxicity. The present study was aimed to determine whether amifostine has an influence on the amount of residual chromosomal damage.
Peripheral lymphocytes of twelve rectal cancer patients who had undergone postoperative radiochemotherapy 2-3 years ago were investigated for residual chromosomal damage using 24-color fluorescence in situ hybridization (24-color FISH). All twelve patients had received a total dose of 55.8 Gy in conventional fractionation of 1.8 Gy and a 120-h continuous infusion of 5-fluorouracil (5-FU) chemotherapy (1,000 mg/m(2) per day) in the 1st and 5th week of irradiation. Seven out of twelve patients had been given additional amifostine on chemotherapy days (500 mg total dose as short i.v. infusion immediately prior to the daily radiation fraction). Cultivation of lymphocytes and 24-color FISH were performed according to standard protocols. 100 metaphases per patient were analyzed for chromosomal aberrations in a blind study.
Analysis of the average number of breaks per mitosis (B/M) revealed an increased amount of residual chromosomal damage in the group treated with amifostine (0.65 B/M [0.32-0.97]) as well as in those treated without amifostine (0.76 B/M [0.31-1.25]). Also the average number of cells containing aberrations per 100 analyzed metaphases was similar (with amifostine: 22.1 [13-32] vs. 24.4 [13-35] without amifostine). The aberration types, occurring as simple translocations, reciprocal translocations, breaks, dicentrics, inversions, rings and complex chromosomal rearrangements, did not show any specific accumulation in one or the other group either.
While there was a significant amifostine-mediated clinical amelioration of normal tissue toxicity, the comparison of residual chromosomal damage 2-3 years after completion of radiochemotherapy was characterized by a high interindividual variation, and no equivalent difference could be detected between the two groups.
氨磷汀是一种放射保护药物，用于在常规分割放疗过程中降低急性放射毒性。在本研究中，氨磷汀用于接受直肠癌辅助放化疗的患者。此前有描述称，额外应用氨磷汀可减轻急性皮肤和肠道毒性。本研究旨在确定氨磷汀是否对残余染色体损伤量有影响。
对12例2 - 3年前接受过术后放化疗的直肠癌患者的外周淋巴细胞，使用24色荧光原位杂交（24色FISH）检测残余染色体损伤。所有12例患者均接受了总量为55.8 Gy的常规分割放疗，每次1.8 Gy，并在放疗的第1周和第5周连续120小时输注5 - 氟尿嘧啶（5 - FU）化疗（每天1000 mg/m²）。12例患者中有7例在化疗日额外给予了氨磷汀（总剂量500 mg，在每日放疗分次前立即进行短时间静脉输注）。淋巴细胞培养和24色FISH按照标准方案进行。在一项盲法研究中，对每位患者的100个中期分裂相进行染色体畸变分析。
对每个有丝分裂期的平均断裂数（B/M）分析显示，接受氨磷汀治疗的组（0.65 B/M [0.32 - 0.97]）以及未接受氨磷汀治疗的组（0.76 B/M [0.31 - 1.25]）中，残余染色体损伤量均增加。同样，每100个分析的中期分裂相中含有畸变的细胞平均数量也相似（接受氨磷汀治疗组：22.1 [13 - 32]，未接受氨磷汀治疗组：24.4 [13 - 35]）。畸变类型包括简单易位、相互易位、断裂、双着丝粒、倒位、环状染色体和复杂染色体重排，在两组中均未显示出任何特定的聚集。
虽然氨磷汀介导的正常组织毒性临床改善显著，但放化疗完成2 - 3年后残余染色体损伤的比较显示个体间差异很大，两组之间未检测到等效差异。
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