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>）作为一种新的在研药物，至今尚未在我院上市，我们无法评价锶89（Sr^<89）后对淋巴细胞的细胞学放射损伤。 >) 疗法，在本研究中使用胞质分裂阻断微核测定 (CBMA) 来缓解转移性骨疾病。因此，我们使用 CBMA 评估了细胞学程度。食道癌患者接受放射治疗（RT）并伴有椎骨的外部照射时，对淋巴细胞造成放射损伤。这种放射治疗可能与骨转移的放射治疗密切相关，放射引起的淋巴细胞染色体损伤应导致细胞增多。方法：我们研究了 12 名接受 RT 治疗的患者，并在治疗后 1 周内收集了患者的分离淋巴细胞。根据 Fenech 和 Morley 的胞质分裂阻断法收获并处理，通过目视检查对每 500 个双核细胞的淋巴细胞微核数量进行了研究。来自 8 名正常志愿者的淋巴细胞接受 0.5 至 2.0 Gy 的剂量照射，并用相同的方法进行研究。 结果：RT 后淋巴细胞的平均数量（平均值±SD）显着增加。 (p<0.05) 与对照受试者相比 (52±10.7 vs. 8.8±1.8) 在一项体外研究中，这些数据符合非阈值、线性剂量反应函数。结论： 淋巴细胞微核诱导的频率相对较低。这种体内放疗支持了这样的论点，即放疗对骨转移疼痛患者的短期非随机损伤可能很小。