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多色荧光原位杂交技术检测放射性碘诱发接受治疗的患者颊黏膜细胞中17cen-p53染色体断裂情况

Multicolour FISH detection of radioactive iodine-induced 17cen-p53 chromosomal breakage in buccal cells from therapeutically exposed patients.

作者信息

Ramírez M J, Puerto S, Galofré P, Parry E M, Parry J M, Creus A, Marcos R, Surrallés J

机构信息

Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

出版信息

Carcinogenesis. 2000 Aug;21(8):1581-6.

Abstract

Simultaneous labelling of 17cen and the p53 locus by multicolour FISH was used to monitor radioactive iodine-induced structural and numerical chromosome abnormalities in buccal cells from 29 hyperthyroidism and thyroid cancer patients sampled before and after therapeutic treatment. This novel methodology allowed the efficient detection of 17p deletions leading to p53 allelic deletions, 17p gains and whole chromosome 17 numerical abnormalities in epithelial cells. Highly significant increases in the frequency of cells with (i) 17p abnormalities (1.8-fold; P < 0.001), including p53 monoallelic deletions (2.1-fold; P < 0.001) and 17p gains (3.5-fold; P < 0.001); (ii) chromosome 17 numerical abnormalities (2-fold; P < 0.001); and (iii) simultaneous 17p breakage and chromosome 17 numerical abnormalities (2.3-fold; P < 0.001), were observed after radioactive iodine treatment. As expected, the major contribution to these increases was detected in hyperthyroidism patients compared with thyroid cancer patients who suffered thyroidectomy before radioactive iodine exposure and, therefore, experienced a rapid elimination of the radioisotope. Considering that both the genetic endpoints and the target tissue are extremely relevant in carcinogenesis, it is suggested that the observed genetic damage could contribute to the reported increase in cancer risk of people therapeutically or accidentally exposed to radioactive iodine.

摘要

采用多色荧光原位杂交技术对17号染色体着丝粒和p53基因座进行同时标记,以监测29例甲状腺功能亢进症和甲状腺癌患者在治疗前后采集的颊黏膜细胞中放射性碘诱导的结构和数目染色体异常情况。这种新方法能够有效检测上皮细胞中导致p53等位基因缺失的17号染色体短臂缺失、17号染色体短臂增加以及17号染色体的整条染色体数目异常。放射性碘治疗后,观察到具有以下情况的细胞频率显著增加:(i)17号染色体短臂异常(增加1.8倍;P<0.001),包括p53单等位基因缺失(增加2.1倍;P<0.001)和17号染色体短臂增加(增加3.5倍;P<0.001);(ii)17号染色体数目异常(增加2倍;P<0.001);(iii)17号染色体短臂断裂和17号染色体数目异常同时出现(增加2.3倍;P<0.001)。正如预期的那样,与在放射性碘暴露前接受甲状腺切除术从而迅速清除放射性同位素的甲状腺癌患者相比,甲状腺功能亢进症患者对这些增加的贡献最大。鉴于遗传终点和靶组织在致癌过程中都极为相关,有人提出,观察到的遗传损伤可能导致了报告中接受放射性碘治疗或意外接触放射性碘的人群癌症风险增加。

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