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

Abstract

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.