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碘-131治疗与染色体损伤:体内剂量效应关系

Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship.

作者信息

Erselcan Taner, Sungu Selma, Ozdemir Semra, Turgut Bulent, Dogan Derya, Ozdemir Ozturk

机构信息

Department of Nuclear Medicine, Cumhuriyet University School of Medicine, P.K. 806 Sivas, Turkey.

出版信息

Eur J Nucl Med Mol Imaging. 2004 May;31(5):676-84. doi: 10.1007/s00259-003-1427-3. Epub 2004 Jan 28.

DOI:10.1007/s00259-003-1427-3
PMID:14747958
Abstract

Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of (131)I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and 5.75+/-2.06, respectively, in the whole group, and these values differed significantly from each other ( P<0.001). In order to perform a quantitative evaluation of the present data and a comparative analysis with the results of previous studies reported in the literature, we defined acute and late effects using a "damage ratio" (DR) and a "recovery ratio" (RR), based on the basal, acute and late data for individual patients. No statistically significant difference was found in the DR between DTC and TTX patients (76.4%+/-11.5% vs 67.6%+/-9.0%), while the mean RR was higher in TTX patients than in the DTC group (75.2%+/-24.4% vs 36.8%+/-13.7%). The DR on the 3rd day was not related to the administered (131)I dose in the whole group, but a negative correlation was found between the (131)I dose and the RR at the 6th month (r=-0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x-28.4x(2)+38.1 ( R(2)=0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of (131)I and DR and RR were obtained with a linear-quadratic model (Y=alpha D+beta D(2)) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient beta to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following (131)I treatment. Further studies are therefore needed to clarify the effect of the negative beta value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of (131)I treatment.

摘要

虽然众所周知辐射会诱发染色体畸变,但对于接受碘-131治疗的患者体内剂量效应关系的信息却很匮乏,且以往研究结果存在争议。在本研究中,采用姐妹染色单体交换(SCE)方法,对15例接受不同剂量(259 - 3700 MBq)碘-131治疗的患者外周淋巴细胞中的急性和晚期染色体损伤(CD)进行了研究,这些患者分别患有甲状腺毒症(TTX)或接受分化型甲状腺癌(DTC)的消融治疗。在治疗前(以评估基础SCE频率)、第3天(以评估急性SCE频率)和6个月后(以评估晚期SCE频率)测定培养的外周淋巴细胞中的SCE频率。全组的基础、急性和晚期SCE频率(均值±标准差)分别为3.19±0.93、10.83±1.72和5.75±2.06,这些值彼此间差异显著(P<0.001)。为了对当前数据进行定量评估并与文献中报道的以往研究结果进行比较分析,我们基于个体患者的基础、急性和晚期数据,使用“损伤率”(DR)和“恢复率”(RR)来定义急性和晚期效应。DTC患者和TTX患者的DR无统计学显著差异(76.4%±11.5%对67.6%±9.0%),而TTX患者的平均RR高于DTC组(75.2%±24.4%对36.8%±13.7%)。第3天的DR与全组所给予的碘-131剂量无关,但在第6个月时碘-131剂量与RR之间发现存在负相关(r = -0.60,P = 0.04)。这种关系的最佳拟合通过线性二次模型获得,即y = 104.89x - 28.4x² + 38.1(R² = 0.51,P = 0.04)。另一方面,与具有可比采样时间的以往研究结果进行比较分析表明,碘-131给药剂量与DR和RR之间关系的最佳拟合是通过线性二次模型(Y = αD + βD²)而非线性模型获得。然而,与体外研究相比存在一个有趣的差异,即我们发现系数β为负值,这表明碘-131治疗后受损淋巴细胞以剂量依赖方式从外周循环中消失。因此,需要进一步研究来阐明负β值对连续内部低LET辐射(如碘-131治疗)生物剂量测定方法的影响。

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