Modulation of radiation-induced chromosomal damage by inhibitors of DNA repair and flow cytometric analysis in ataxia telangiectasia cells with 'intermediate radiosensitivity'

Mutagenesis
A AntocciaC Tanzarella

Abstract

The relationship between repair processes and chromosomal aberrations and X-ray-induced cell cycle perturbations were investigated in ataxia telangiectasia (AT) cells with 'intermediate' (AT-INT) and 'classical' radiosensitivity. In the cytogenetic experiments, three AT-INT lymphoblastoid cell lines were X-irradiated in G2-phase and incubated in the presence of inhibitors of DNA polymerases alpha/delta/epsilon (cytosine arabinoside, aphidicolin, 10% v/v DMSO), ribonucleotide reductase (hydroxyurea) and presumed inhibitors of protein kinases (caffeine). Flow cytometric analysis was performed in cells harvested 20 h after irradiation and stained with either propidium iodide or antibody against 5-bromodeoxiuridine in order to investigate cell cycle distribution focusing on G2/Mphase accumulation. From our data it appears that: (i) chromosomal sensitivity to radiation in AT does not always reflect clinical features; (ii) the effects of DNA repair inhibitors are inversely correlated with chromosomal radiosensitivity; and (iii) radiation-induced G2/M phase accumulation is a feature of AT cells and not necessarily correlated with cellular and chromosomal sensitivity to ionizing radiation.

Citations

Apr 29, 1998·American Journal of Human Genetics·S GiladA Bar-Shira
Jun 5, 2001·Nature Reviews. Genetics·H Joenje, K J Patel
May 31, 2003·Nature Reviews. Genetics·Santiago F Elena, Richard E Lenski
Oct 31, 1996·Nature·D W Mount
Dec 17, 2005·Nature Reviews. Microbiology·Tonje Davidsen, Tone Tønjum
Jun 21, 2017·The FEBS Journal·Rosa PennisiAlessandra di Masi

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