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癌症患者放疗后淋巴细胞染色体不稳定性延迟。

Delayed chromosomal instability in lymphocytes of cancer patients after radiotherapy.

机构信息

Radiation Cytogenetics Laboratory, Institute for Medical Radiology AMS of Ukraine, Kharkiv, Ukraine.

出版信息

Int J Radiat Biol. 2010 Apr;86(4):271-82. doi: 10.3109/09553000903564026.

Abstract

PURPOSE

To assess possible delayed chromosomal instability (DCI) expressed as elevated chromatid breakage in cells containing previously formed chromosome type aberrations in cultured blood lymphocytes of cancer patients after radiotherapy (RT).

MATERIALS AND METHODS

Twenty patients treated for uterine cancer with external Co(60) RT, without chemotherapy, were selected. Blood was taken before, 1-2 days after RT and one year later. Lymphocytes were cultured for 50 and 100 h. Metaphases were stained with fluorescence-plus-Giemsa and analysed for chromosome and chromatid aberrations in 1st (M1) and 3rd plus later (M3+) mitoses.

RESULTS

RT caused a significant increase of radiation-specific chromosome aberrations in patients' lymphocytes together with DCI, which was observed as an excessive yield of cells containing both chromosome and chromatid aberrations (defined as C(acs&act)). This DCI passed successfully through mitoses in vitro, and at the end of RT a mean yield of 'extra' C(acs&act) was 3 x 10(-3) x cell(-1) amongst either M1 or M3+ cells. At the end of RT and one year later DCI in M1 lymphocytes appeared at random amongst patients, but some inter-individual variation was found for DCI presence in M3+ cells at both post-irradiation samplings. As time passed, the mean yield of lymphocytes exhibiting DCI decreased in vivo and one year after RT reached the pre-treatment level of 1 x 10(-3) x cell(-1).

CONCLUSIONS

DCI was demonstrated in descendants of human lymphocytes after therapeutic irradiation. The effect diminished one year later, suggesting that the progeny of patients' irradiated stem cells did not produce new daughter lymphocytes exhibiting DCI during the studied post-irradiation period.

摘要

目的

评估癌症患者在接受放射治疗(RT)后培养的血液淋巴细胞中,先前形成的染色体类型畸变细胞中出现的升高的染色单体断裂是否存在延迟的染色体不稳定性(DCI)。

材料与方法

选择 20 例接受子宫癌外 Co(60)RT 治疗且未接受化疗的患者。在 RT 前、RT 后 1-2 天和 1 年后采集血液。淋巴细胞培养 50 和 100 小时。用荧光加吉姆萨染色对第 1 次(M1)和第 3 次加后期(M3+)有丝分裂中的染色体和染色单体畸变进行分析。

结果

RT 导致患者淋巴细胞中出现明显的辐射特异性染色体畸变,同时伴有 DCI,表现为同时含有染色体和染色单体畸变的细胞过度产生(定义为 C(acs&act))。这种 DCI 在体外成功地通过有丝分裂,在 RT 结束时,无论是 M1 细胞还是 M3+细胞,“额外”的 C(acs&act)的平均产量为 3×10(-3)×细胞(-1)。在 RT 结束时和 1 年后,M1 淋巴细胞中的 DCI 在患者中随机出现,但在两次辐射后采样中均发现 M3+细胞中 DCI 的存在存在个体间差异。随着时间的推移,体内表现出 DCI 的淋巴细胞的平均产量减少,在 RT 后 1 年达到治疗前的 1×10(-3)×细胞(-1)水平。

结论

在经过治疗性照射的人类淋巴细胞后代中发现了 DCI。1 年后,这种效应减弱,表明在研究的照射后期间,患者照射的干细胞的后代没有产生新的具有 DCI 的子代淋巴细胞。

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