Evaluation of radiotoxicity after strontium-89 therapy for bone metastases using the micronucleus assay.

使用微核测定评估锶 89 治疗骨转移后的放射毒性。

• 批准号: 12670857
• 负责人: WATANABE Naoto
• 金额: $ 2.18万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670857/
• 关键词: Lymphocyte; micronucleus assay; Radiation damage; irradiation

It is unexpected that strontium-89 (Sr^<89>), as a new investigational drug, is not clinically available in our hospital until now. We can not evaluate the cytological radiation damage to lymphocytes after strontium-89 (Sr^<89>) therapy, which have a role in palliating metastatic bone diseases, using the cytokinesis-blocked micronucleus assay (CBMA) in the present study. Therefore, using CBMA we evaluated the degree of cytological radiation damage to lymphocytes in esophageal cancer patients with radiation therapy (RT) accompanying with external irradiation consequently for vertebral bones. This RT may be closely correlated to RT for bone metastases. The chromosomal damage to lymphocytes induced by irradiation should result in augmentation of the cells with micronuclei. Methods : We studied 12 patients with esophageal cancer, who were treated with RT. Isolated lymphocytes collected from patients within 1 week after therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. Micronucleus number of lymphocytes micronuclei per 500 binucleated cells was scored by visual inspection. As controls, lymphocytes from the same patients before therapy were also studied. In an in vitro study, lymphocytes from eight normal volunteers were exposed with doses varying from 0.5 to 2.0 Gy and studied with the same method. Results : The mean number (mean±SD) of lymphocytes after RT was significantly increased (p<0.05) as compared to control subjects (52±10.7 vs. 8.8±1.8). In an in vitro study, these data fit a nonthreshold, linear dose-response function.Conclusions : The relatively low frequency of lymphocyte micronuclei induced by this RT in vivo supported the contention that short-term non-stochastic damage with RT in patients with painful bone metastases may be minimal.

令人意外的是，锶-89 （Sr^<89>）作为一种新的研究药物，至今尚未在我院临床使用。在本研究中，我们不能使用细胞分裂阻断微核测定（CBMA）来评估锶-89 （Sr^<89>）治疗后淋巴细胞的细胞学辐射损伤，而锶-89在缓解转移性骨病中起作用。因此，我们使用CBMA评估食管癌患者放射治疗（RT）伴外照射后淋巴细胞的细胞学损伤程度。这个RT可能与骨转移的RT密切相关。照射对淋巴细胞的染色体损伤可导致微核细胞增多。方法：对12例食管癌患者进行rt治疗，治疗后1周内收集患者分离淋巴细胞，采用Fenech和Morley细胞分裂阻断法进行治疗。目测每500个双核细胞中淋巴细胞微核数。作为对照，同样的患者治疗前的淋巴细胞也被研究。在一项体外研究中，来自8名正常志愿者的淋巴细胞暴露在0.5至2.0 Gy的剂量范围内，并采用相同的方法进行研究。结果：与对照组（52±10.7 vs. 8.8±1.8）相比，放疗后淋巴细胞平均数目（mean±SD）显著增加（p<0.05）。在体外研究中，这些数据符合非阈值的线性剂量-反应函数。结论：这种放射疗法在体内诱导淋巴细胞微核的频率相对较低，这支持了一种观点，即放射疗法对疼痛性骨转移患者的短期非随机损伤可能很小。