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1 September 2001 Chromosome Nondisjunction and Loss Induced by Protons and X Rays in Primary Human Fibroblasts: Role of Centromeres in Aneuploidy
A. Sgura, A. Antoccia, R. Cherubini, C. Tanzarella
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Abstract

Sgura, A., Cherubini, A. R. and Tanzarella, C. Chromosome Nondisjunction and Loss Induced by Protons and X Rays in Primary Human Fibroblasts: Role of Centromeres in Aneuploidy. Radiat. Res. 156, 225–231 (2001).

To study the origin of micronuclei induced in human primary fibroblasts by low-energy protons (7.7 and 28.5 keV/μm) and X rays, we have developed a combined antikinetochore-antibody (CREST) and FISH staining with pancentromeric probes. This technique allowed us to analyze the integrity of the kinetochore and centromeric DNA structures and to assess their role in induced aneuploidy. The effect of LET on radiation-induced chromosome nondisjunction was studied in binucleated cells with centromeric-specific DNA probes for chromosomes 7 and 11. Our results indicate that, though more than 90% of radiation-induced micronuclei were CREST/FISH, 28.5 keV/μm protons and X rays were also able to induce statistically significant increases in the number of micronuclei that were CREST/FISH and CREST /FISH , respectively. One interpretation of these results could be that the protons induced chromosome loss by kinetochore detachment or by breakage in the centromeric DNA region, whereas X rays induced aneuploidy through a non-DNA damage mechanism. Nondisjunction appears to be a far more important mechanism leading to radiation-induced aneuploidy. Irrespective of the higher frequency of micronuclei induced by 28.5 keV/μm protons, the frequency of chromosome loss was markedly higher for X rays than for 28.5 keV/μm protons, strengthening the hypothesis that non-DNA targets, such as components of the mitotic spindle apparatus, may be involved in aberrations in chromosome segregation after X irradiation.

A. Sgura, A. Antoccia, R. Cherubini, and C. Tanzarella "Chromosome Nondisjunction and Loss Induced by Protons and X Rays in Primary Human Fibroblasts: Role of Centromeres in Aneuploidy," Radiation Research 156(3), 225-231, (1 September 2001). https://doi.org/10.1667/0033-7587(2001)156[0225:CNALIB]2.0.CO;2
Received: 16 January 2001; Accepted: 1 May 2001; Published: 1 September 2001
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