Reduced inhibition of replicon initiation and chain elongation by neocarzinostatin in skin fibroblasts from patients with ataxia telangiectasia.
Cells from patients with the genetic disease ataxia telangiectasia are hypersensitive to the DNA-breaking agents X-rays, bleomycin and neocarzinostatin, and show reduced inhibition of DNA synthesis after treatment with these agents, as compared to normal cells. The rate of replicon initiation and chain elongation was measured shortly after brief exposure of two normal and two ataxia telangiectasia fibroblast strains to low doses (0.10-0.30 microgram/ml) of neocarzinostatin, by means of alkaline sucrose gradient analysis. Neocarzinostatin was found to inhibit both initiation and elongation, and both components of DNA synthesis were more resistant to this inhibition in the A-T strains.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001260:Ataxia Telangiectasia / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D012093:Replicon / Q000187:drug effects*; D012867:Skin / Q000378:metabolism; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D004247:DNA; D009353:Zinostatin