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

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.