The response of normal and ataxia-telangiectasia cells to bleomycin: relationships between chromosome damage, cell cycle delay and cell killing.
In agreement with our earlier observation (Scott and Zampetti-Bosseler, 1982) on X-irradiated normal and ataxia-telangiectasia (A-T) fibroblasts, we now report that after bleomycin or neocarzinostatin treatment also, A-T cells exhibit less G2 delay than normal cells. We confirm that A-T cells sustain more chromosome damage and lethality than normal cells after bleomycin. These observations support the hypothesis (Painter and Young, 1980) that A-T cells are defective in the recognition of certain lesions which normally lead to delays in progression through the cell cycle, during which they are repaired, and which, if unrepaired, lead to cell-lethal chromosome damage. However, we find that after bleomycin, as opposed to X-rays, the contribution of this type of lesion to cell death is minimal. The predominant lesions leading to cell death after bleomycin are not manifested at chromosome aberrations and do not lead to G2 delay or DNA-synthesis inhibition. A-T cells are defective in the recognition and/or repair of both types of lesion.
Zampetti-Bosseler
F
F
Scott
D
D
D001260:Ataxia Telangiectasia / Q000235:genetics*; D001761:Bleomycin / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000528:radiation effects; D006801:Humans; D007399:Interphase / Q000528:radiation effects; D009154:Mutation / Q000187:drug effects; D009353:Zinostatin / Q000633:toxicity
D001761:Bleomycin; D009353:Zinostatin