Transmission of Induced Chromosomal Aberrations through Successive Mitotic Divisions in Human Lymphocytes after In Vitro and In Vivo Radiation

体外和体内辐射后,人类淋巴细胞中通过连续有丝分裂传播诱发的染色体畸变

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作者:Akram Kaddour, Bruno Colicchio, Diane Buron, Elie El Maalouf, Eric Laplagne, Claire Borie, Michelle Ricoul, Aude Lenain, William M Hempel, Luc Morat, Mustafa Al Jawhari, Corina Cuceu, Leonhard Heidingsfelder, Eric Jeandidier, Georges Deschênes, Alain Dieterlen, Michèle El May, Theodore Girinsky, Ann

Abstract

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.

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