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.
Antoccia
A
A
Dipartimento di Genetica e Biologia Molecolare, Università La Sapienza, Rome, Italy.
Chessa
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L
Ricordy
R
R
Tanzarella
C
C
D016590:Aphidicolin / Q000494:pharmacology; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000528:radiation effects*; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D016193:G1 Phase / Q000187:drug effects / Q000528:radiation effects; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects; D019384:Nucleic Acid Synthesis Inhibitors; D011836:Radiation Tolerance / Q000235:genetics; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors; D014965:X-Rays
D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine; D016590:Aphidicolin; D006918:Hydroxyurea; D004121:Dimethyl Sulfoxide