title: Chromosomal sensitivity to clastogenic agents and cell cycle perturbations in Nijmegen breakage syndrome lymphoblastoid cell lines.
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 gamma 1I, 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.
authors.affiliation: Dipartimento di Biologia, Terza Università, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Antoccia
authors.forename: R
authors.initials: R
authors.lastname: Ricordy
authors.forename: P
authors.initials: P
authors.lastname: Maraschio
authors.forename: S
authors.initials: S
authors.lastname: Prudente
authors.forename: C
authors.initials: C
authors.lastname: Tanzarella
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line / Q000187:drug effects / Q000528:radiation effects; D019457:Chromosome Breakage; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008940:Mitotic Index / Q000528:radiation effects; D011836:Radiation Tolerance; D012854:Sister Chromatid Exchange; D013577:Syndrome
chemical_list: D004247:DNA