Impaired p53-mediated DNA damage response, cell-cycle disturbance and chromosome aberrations in Nijmegen breakage syndrome lymphoblastoid cell lines.

Abstract:

PURPOSE:To investigate the p53 ionizing radiation-induced response, G1/S cell-cycle block and cytogenetic damage in Nijmegen breakage syndrome (NBS) cells characterized by different haplotypes. MATERIAL AND METHODS:Lymphoblastoid cell lines derived from three normals, five NBS and two ataxia telangiectasia (AT) individuals were treated with moderate doses of X-rays and changes in the p53 response were studied by dose-response and time-course experiments. Multiparametric flow cytometry analysis of bromodesoxyuridine-incorporated cells was carried out to analyse G1/S checkpoint alterations. Cytogenetic damage induced by 2 Gy radiation was assessed in cells harvested 28 h later. RESULTS:Comparison of mean values of p53 accumulation in NBS, AT and control cells indicated that protein induction in NBS cells was between normal and AT cells. Cell-cycle experiments showed a markedly reduced S-phase fraction in irradiated samples of normal cell lines, while NBS, and particularly AT cells, showed less reduction in S-phase fraction. Irrespective of differences in p53 induction and G1/S block, chromatid-type aberrations were induced at a comparable level in both syndromes, while being almost absent in normal cells. CONCLUSIONS:The data suggested that failure of NBS cells to initiate cell-cycle delay cannot account alone for their extreme sensitivity to radiation.

journal_name

Int J Radiat Biol

authors

Antoccia A,Stumm M,Saar K,Ricordy R,Maraschio P,Tanzarella C

doi

10.1080/095530099140221

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

583-91

issue

5

eissn

0955-3002

issn

1362-3095

journal_volume

75

pub_type

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