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Sci Rep. 2017 Jun 12;7(1):3291. doi: 10.1038/s41598-017-03198-7.

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

Author information

1
Laboratory of Radiobiology and Oncology and PROCyTOX, DRF, CEA, Paris-Saclay, France.
2
Tunis El Manar University, School of Medicine, Tunis, Tunisia.
3
Laboratoire MIPS Groupe IMTI Université de Haute-Alsace, Mulhouse, France.
4
Pole Concept, Paris, France.
5
APHP-Hopital Paul Brousse Université Paris Sud/ESteam Paris Inserm UMR 935, Villejuif, France.
6
MetaSystems GmbH, Robert-Bosch-Str. 6 D-68804, Altlussheim, Germany.
7
Service de Génétique Groupe Hospitalier de la Région de Mulhouse et Sud Alsace, 68070, Mulhouse, France.
8
Nephrology Department, APHP-Hopital Robert Debré, Paris, France.
9
Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
10
Department of Hematology, Gustave Roussy cancer Campus, Villejuif, France.
11
Laboratory of Radiobiology and Oncology and PROCyTOX, DRF, CEA, Paris-Saclay, France. radhia.mkacher@gmail.com.
12
Cell Environment, Paris, France. radhia.mkacher@gmail.com.

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.

PMID:
28607452
PMCID:
PMC5468351
DOI:
10.1038/s41598-017-03198-7
[Indexed for MEDLINE]
Free PMC Article

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