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内源性放射性碘暴露诱导的简单、复杂和克隆性染色体易位的检测:25年后的细胞遗传学随访病例研究

Detection of Simple, Complex, and Clonal Chromosome Translocations Induced by Internal Radioiodine Exposure: A Cytogenetic Follow-Up Case Study after 25 Years.

作者信息

Livingston Gordon K, Ryan Terri L, Smith Tammy L, Escalona Maria B, Foster Alvis E, Balajee Adayabalam S

出版信息

Cytogenet Genome Res. 2019;159(4):169-181. doi: 10.1159/000504689. Epub 2019 Dec 17.

Abstract

Here, we report the findings of a 25-year cytogenetic follow-up study on a male patient who received 2 rounds of radioiodine treatment within a span of 26 months (1.78 GBq in 1992 and 14.5 GBq in 1994). The patient was 34 years old with a body mass index of 25 at the time of the first radioiodine treatment. Multicolor FISH and multicolor banding (mBAND) techniques performed on the patient detected inter- and intrachromosomal exchanges. Although the frequency of chromosome translocations remained essentially the same as reported in our earlier study (0.09/cell), the percentage of reciprocal (balanced) translocations increased from 54.38 to 80.30% in the current study. In addition to simple chromosome translocations, complex exchanges (0.29%) involving more than 2 chromosomes were detected for the first time in this patient. Strikingly, a clonal translocation involving chromosomes 14 and 15, t(14p;15q), was found in 7 of the 677 cells examined (1.03%). The presence of complex and clonal translocations indicates the onset of chromosomal instability induced by internal radioiodine exposure. mBAND analysis using probes specific for chromosomes 1, 2, 4, 5, and 10 revealed 5 inversions in a total of 717 cells (0.69%), and this inversion frequency is several-fold higher than the baseline frequency reported in healthy individuals using the classical G-banding technique. Collectively, our study suggests that stable chromosome aberrations such as translocations and inversions can be useful not only for retrospective biodosimetry but also for long-term monitoring of chromosomal instability caused by past radioiodine exposure.

摘要

在此,我们报告了一项针对一名男性患者的长达25年的细胞遗传学随访研究结果。该患者在26个月内接受了2轮放射性碘治疗(1992年为1.78GBq,1994年为14.5GBq)。首次放射性碘治疗时,患者34岁,体重指数为25。对该患者进行的多色荧光原位杂交(FISH)和多色显带(mBAND)技术检测到了染色体间和染色体内的交换。尽管染色体易位的频率与我们早期研究报告的基本相同(0.09/细胞),但在本研究中,相互(平衡)易位的百分比从54.38%增加到了80.30%。除了简单的染色体易位外,该患者首次检测到涉及2条以上染色体的复杂交换(0.29%)。引人注目的是,在检查的677个细胞中有7个(1.03%)发现了涉及14号和15号染色体的克隆性易位t(14p;15q)。复杂和克隆性易位的存在表明内部放射性碘暴露导致了染色体不稳定性的发生。使用针对1、2、4、5和10号染色体的特异性探针进行的mBAND分析在总共717个细胞中发现了5个倒位(0.69%),该倒位频率比使用经典G显带技术在健康个体中报告的基线频率高几倍。总体而言,我们的研究表明,诸如易位和倒位等稳定的染色体畸变不仅可用于回顾性生物剂量测定,还可用于长期监测过去放射性碘暴露引起的染色体不稳定性。

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