Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells

Mutat Res. 1994 Oct 1;310(1):1-13. doi: 10.1016/0027-5107(94)90004-3.


Individuals heterozygous for ataxia telangiectasia (AT) appear clinically normal but have a 2-3-fold overall excess risk of cancer. Various approaches have been used to identify AT heterozygotes, however, the results are ambiguous. We recently reported that AT homozygotes exhibit more initial chromosome damage after irradiation than normal cells despite identical levels of DNA double strand breaks (DSBs) as well as a reduced fast repair component at both the DNA and chromosome levels. To determine whether AT heterozygotes exhibit the AT or normal cellular phenotype, we compared four AT heterozygote lymphoblastoid cell lines with normal control and AT homozygote lymphoblastoid cells with regard to cell survival, initial levels of damage, and repair at the DNA and chromosome levels after gamma-irradiation in G1, S, and G2 phase (estimated by neutral DNA filter elution and premature chromosome condensation). There was no significant difference in survival, induction and repair of DNA DSBs, or chromosome repair between AT heterozygote and normal cells. In contrast, all four AT heterozygote cell lines showed increased levels of chromosome damage; G1 phase cells showed intermediate levels and G2 phase cells showed levels equivalent to the AT homozygote phenotype. These results suggest that premature chromosome condensation may be useful for detecting AT heterozygotes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / pathology
  • CHO Cells
  • Cell Cycle
  • Cell Line, Transformed
  • Cell Survival
  • Chromosome Aberrations*
  • Chromosomes, Human*
  • Cricetinae
  • DNA Damage
  • DNA Repair*
  • Female
  • Gamma Rays
  • Heterozygote
  • Homozygote
  • Humans
  • Male