G2 chromosomal radiosensitivity in fibroblasts of ataxia-telangiectasia heterozygotes and a Li-Fraumeni syndrome patient with radioresistant cells.

Abstract

PURPOSE: To investigate whether the good discrimination we previously observed between ataxia-telangiectasia (A-T) heterozygotes and normal donors for induction of chromosome aberrations by X-rays in G2 lymphocytes is also seen in G2 fibroblasts. Also to investigate the G2 radiosensitivity of a patient with the cancer-prone Li-Fraumeni syndrome (LFS) whose fibroblasts are resistant to the lethal effects of radiation. MATERIALS AND METHODS: Fibroblasts were exposed to 0.5 Gy X-rays and harvested for metaphase analysis 90 min later. RESULTS: Four A-T heterozygote cell strains were all more sensitive than seven normal controls. The LFS strain with a germline TP53 mutation was twice as sensitive as the mean control value. CONCLUSIONS: Although chromosomal, radiosensitivity is seen in A-T heterozygotes and LFS cells, the former are radiosensitive and the latter radioresistant to cell killing. Repair defects may predominate in A-T heterozygotes, inadequate genome surveillance in LFS cells.