Enhanced levels of radiation-induced G2 phase delay in ataxia telangiectasia heterozygotes.

Ataxia telangiectasia (AT) is a multiform genetic disease characterized by immunodeficiency, cerebellar abnormalities, and cancer predisposition. Heterozygotes also have an increased risk of developing several different cancers. It has been estimated that as many as 18% of all patients with breast cancer, the cancer most clearly associated with AT heterozygotes, may be carriers of the AT gene. We describe an assay for AT heterozygotes that relies on the previous observation that cells from AT homozygotes show a greater and more prolonged radiation-induced accumulation in the G2 phase of the cell cycle than do normal controls. We showed that all 6 A-T heterozygotes show a greater extent of G2 phase delay at different times postirradiation than do controls. The degree of accumulation was less than that observed in AT homozygotes. Only two of 22 controls showed overlap with heterozygotes at 18 hours postirradiation, and that number was reduced to one at the 24-hour point. As a group, AT heterozygotes were intermediate between controls and AT homozygotes at both time points after irradiation. This assay is relatively simple and reliable and can be performed in any laboratory with access to both Epstein-Barr virus (EBV) for transformation of lymphocytes and a fluorescence-activated cell analyzer.