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The role of telomere length modulation in delayed chromosome instability induced by ionizing radiation in human primary fibroblasts
Author(s) -
Berardinelli Francesco,
Antoccia Antonio,
Buonsante Rossella,
Gerardi Silvia,
Cherubini Roberto,
Nadal Viviana De,
Tanzarella Caterina,
Sgura Antonella
Publication year - 2013
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.21761
Subject(s) - telomere , chromosome instability , chromosome , anaphase , ionizing radiation , biology , genome instability , mitosis , microbiology and biotechnology , irradiation , genetics , dna damage , dna , gene , physics , nuclear physics
Telomere integrity is important for chromosome stability. The main objective of our study was to investigate the relationship between telomere length modulation and mitotic chromosome segregation induced by ionizing radiation in human primary fibroblasts. We used X‐rays and low‐energy protons because of their ability to induce different telomeric responses. Samples irradiated with 4 Gy were fixed at different times up to 6 days from exposure and telomere length, anaphase abnormalities, and chromosome aberrations were analyzed. We observed that X‐rays induced telomere shortening in cells harvested at 96 hrs, whereas protons induced a significant increase in telomere length at short as well as at long harvesting times (24 and 96 hrs). Consistent with this, the analysis of anaphase bridges at 96 hrs showed a fourfold increase in X‐ray‐ compared with proton‐irradiated samples, suggesting a correlation between telomere length/dysfunction and chromosome missegregation. In line with these findings, the frequency of dicentrics and rings decreased with time for protons whereas it remained stable after X‐rays irradiation. Telomeric FISH staining on anaphases revealed a higher percentage of bridges with telomere signals in X‐ray‐treated samples than that observed after proton irradiation, thus suggesting that the aberrations observed after X‐ray irradiation originated from telomere attrition and consequent chromosome end‐to‐end fusion. This study shows that, beside an expected “early” chromosome instability induced shortly after irradiation, a delayed one occurs as a result of alterations in telomere metabolism and that this mechanism may play an important role in genomic stability. Environ. Mol. Mutagen. 54:172–179, 2013. © 2013 Wiley Periodicals, Inc.