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

Mutagenesis. 1995 Nov;10(6):523-9. doi: 10.1093/mutage/10.6.523.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aphidicolin / pharmacology
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / pathology
  • Cell Cycle / drug effects*
  • Cell Cycle / radiation effects
  • Cells, Cultured
  • Chromosome Aberrations
  • Chromosomes, Human / radiation effects*
  • Cytarabine / pharmacology
  • DNA Damage / radiation effects
  • DNA Repair / drug effects*
  • DNA Repair / radiation effects*
  • Dimethyl Sulfoxide / pharmacology
  • Flow Cytometry / methods
  • G1 Phase / drug effects
  • G1 Phase / radiation effects
  • G2 Phase / drug effects
  • G2 Phase / radiation effects
  • Humans
  • Hydroxyurea / pharmacology
  • Lymphocytes / cytology
  • Lymphocytes / radiation effects
  • Nucleic Acid Synthesis Inhibitors
  • Radiation Tolerance / genetics
  • S Phase / drug effects
  • S Phase / radiation effects
  • Time Factors
  • X-Rays

Substances

  • Nucleic Acid Synthesis Inhibitors
  • Cytarabine
  • Aphidicolin
  • Hydroxyurea
  • Dimethyl Sulfoxide