Chromosomal sensitivity to clastogenic agents and cell cycle perturbations in Nijmegen Breakage Syndrome lymphoblastoid cell lines

A. Antoccia, R. Ricordy, P. Maraschio, S. Prudente, C. Tanzarella

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Abstract

The relationship between chromosomal breakage and perturbations of cell cycle progression was investigated in lymphoblastoid cell lines established from a healthy donor, two subjects affected by Nijmegen Breakage Syndrome (NBS) and an ataxia-telangiectasia (AT) patient. The cytogenetic analysis revealed a similar chromosomal hypersensitivity in both NBS and AT cells exposed in the G1 phase to 200 cGy X-rays or in G2 to 15-30 cGy. Similarly, no differences were observed in the frequency of chromatid-type aberrations induced in G2 by 1-2 pg/ml calicheamicin γ1(I), a DNA double-strand break inducer. In addition, as observed in AT cells, the rate of G2 radiation-induced chromosomal damage was less enhanced in NBS than in control cells following 3-h incubation with inhibitors of DNA synthesis/repair (cytosine arabinoside, aphidicolin, DMSO, hydroxyurea, caffeine). This is suggestive of an altered DNA lesion-processing pathway common to both syndromes. Despite the close resemblance of cellular phenotypes in the two syndromes, the analysis of mitotic indices carried out at 2 and 4 h postirradiation indicated that NBS sustained a G2-delay greater than that observed in AT cells. Furthermore, the flow cytometric analysis of 50-300 cGy irradiated cells at 10 and 20 h before harvesting showed that NBS cells sustained a G2/M phase arrest markedly lower than AT cells. Our data indicate that NBS and AT gene products are involved in a common pathway of radiation-induced chromosomal damage, but in a different one for cell cycle control after irradiation.

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalInternational Journal of Radiation Biology
Volume71
Issue number1
DOIs
Publication statusPublished - 1997

Fingerprint

Nijmegen Breakage Syndrome
Ataxia Telangiectasia
ataxia
cultured cells
cell cycle
Cell Cycle
Cells
cell lines
Cell Line
perturbation
cycles
DNA
sensitivity
cells
Caffeine
Radiation
deoxyribonucleic acid
Aberrations
Repair
Aphidicolin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Nuclear Energy and Engineering
  • Radiation

Cite this

Chromosomal sensitivity to clastogenic agents and cell cycle perturbations in Nijmegen Breakage Syndrome lymphoblastoid cell lines. / Antoccia, A.; Ricordy, R.; Maraschio, P.; Prudente, S.; Tanzarella, C.

In: International Journal of Radiation Biology, Vol. 71, No. 1, 1997, p. 41-49.

Research output: Contribution to journalArticle

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