INCREASED INITIAL LEVELS OF CHROMOSOME-DAMAGE AND HETEROGENEOUS CHROMOSOME REPAIR IN ATAXIA-TELANGIECTASIA HETEROZYGOTE CELLS

Individuals heterozygous for ataxia telangiectasia (AT) appear clinica lly normal but have a 2-3-fold overall excess risk of cancer. Various approaches have been used to identify AT heterozygotes, however the re sults are ambiguous. We recently reported that AT homozygotes exhibit more initial chromosome damage after irradiation than normal cells des pite identical levels of DNA double strand breaks (DSBs) as well as a reduced fast repair component at both the DNA and chromosome levels. T o 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 regar d to cell survival, initial levels of damage, and repair at the DNA an d chromosome levels after gamma-irradiation in G1, S, and G2 phase (es timated by neutral DNA filter elution and premature chromosome condens ation). 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 intermedi ate levels and G2 phase cells showed levels equivalent to the AT homoz ygote phenotype. These results suggest that premature chromosome conde nsation may be useful for detecting AT heterozygotes.