Comparison of kinetics of X-ray-induced cell killing in normal, ataxia telangiectasia and hereditary retinoblastoma fibroblasts.

Survival, cumulative labeling indices and chromosomal aberrations were studied in normal, ataxia telangiectasia (AT) and hereditary retinoblastoma fibroblasts after X-irradiation during density-inhibition of growth and immediate release by subculture to low density. The D0 of the survival curves were: normal strains, 150-160 rad; Retinoblastoma strains AG 1880, 95 rad; AG 1978, 40-50 rad (sensitive fraction); AT5BI, 45 rad. Mainly chromosome-type Aberrations were induced in normal and retinoblastoma cells. The frequency of X-ray-induced chromosomal aberrations was much higher in AT5BI cells, and 33-45% were of the chromatid type. Normal and retinoblastoma cells showed a measureable X-ray induced G1 delay before entering S. In addition, a fraction of the cells showed an apparently irreversible G1 block; these cells did not initiate DNA synthesis up to 120 h post-irradiation and subculture. The G1 block was much more marked in retinoblastoma cells; after 400 rad about 70% of retinoblastoma cells did not enter S as compared with only 20% of normal cells. Neither a G1 delay nor a G1 block was observed in AT cells irradiated with up to 400 rad despite their hypersensitivity to cell killing by X-rays and evidence of severe chromosome damage. These results suggest different mechanisms for the X-ray hypersensitivity of AT and retinoblastoma cells.