title: Impaired p53-mediated DNA damage response, cell-cycle disturbance and chromosome aberrations in Nijmegen breakage syndrome lymphoblastoid cell lines.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Genetics and Molecular Biology, University La Sapienza, Rome, Italy. antoccia@bio.uniroma3.it
authors.forename: A
authors.initials: A
authors.lastname: Antoccia
authors.forename: M
authors.initials: M
authors.lastname: Stumm
authors.forename: K
authors.initials: K
authors.lastname: Saar
authors.forename: R
authors.initials: R
authors.lastname: Ricordy
authors.forename: P
authors.initials: P
authors.lastname: Maraschio
authors.forename: C
authors.initials: C
authors.lastname: Tanzarella
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics*; D013577:Syndrome; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014965:X-Rays
chemical_list: D016159:Tumor Suppressor Protein p53; D004247:DNA