Laboratory of Radiobiology and Oncology and PROCyTOX, DRF, CEA, Paris-Saclay, France.
Tunis El Manar University, School of Medicine, Tunis, Tunisia.
Sci Rep. 2017 Jun 12;7(1):3291. doi: 10.1038/s41598-017-03198-7.
The mechanisms behind the transmission of chromosomal aberrations (CA) remain unclear, despite a large body of work and major technological advances in chromosome identification. We reevaluated the transmission of CA to second- and third-division cells by telomere and centromere (TC) staining followed by M-FISH. We scored CA in lymphocytes of healthy donors after in vitro irradiation and those of cancer patients treated by radiation therapy more than 12 years before. Our data demonstrate, for the first time, that dicentric chromosomes (DCs) decreased by approximately 50% per division. DCs with two centromeres in close proximity were more efficiently transmitted, representing 70% of persistent DCs in ≥M3 cells. Only 1/3 of acentric chromosomes (ACs), ACs with four telomeres, and interstitial ACs, were paired in M2 cells and associated with specific DCs configurations. In lymphocytes of cancer patients, 82% of detected DCs were characterized by these specific configurations. Our findings demonstrate the high stability of DCs with two centromeres in close proximity during cell division. The frequency of telomere deletion increased during cell cycle progression playing an important role in chromosomal instability. These findings could be exploited in the follow-up of exposed populations.
染色体畸变（CA）的传递机制仍不清楚，尽管在染色体鉴定方面已经有大量的工作和重大的技术进步。我们通过端粒和着丝粒（TC）染色后进行 M-FISH 重新评估了 CA 向第二和第三分裂细胞的传递。我们对体外照射后的健康供体的淋巴细胞和 12 年前接受放射治疗的癌症患者的淋巴细胞进行了 CA 评分。我们的数据首次表明，双着丝粒染色体（DCs）每分裂减少约 50%。两个着丝粒紧密靠近的 DCs 更容易传递，代表≥M3 细胞中持续存在的 DCs 的 70%。只有 1/3 的无着丝粒染色体（ACs）、具有四个端粒的 ACs 和间质 ACs 在 M2 细胞中配对，并与特定的 DC 构型相关。在癌症患者的淋巴细胞中，82%检测到的 DCs 具有这些特定的构型。我们的研究结果表明，在细胞分裂过程中，两个着丝粒紧密靠近的 DCs 具有很高的稳定性。随着细胞周期的进展，端粒缺失的频率增加，在染色体不稳定性中起着重要作用。这些发现可用于受照射人群的随访。
