Effects of the DNA strand-cleaving antitumor agent, streptonigrin, on ataxia telangiectasia cells.
Cells from patients with ataxia telangiectasia (A-T) were shown to be more sensitive to streptonigrin than were cells from normal individuals. A linear dose-dependent cell survival was observed for both normal and A-T cells exposed to streptonigrin (up to 1.5 ng/ml) for 3-hr, with the A-T cells being about twice as sensitive as were the normal cells (Do approximately 0.25 ng compared with Do approximately 0.5 ng). The extreme toxicity of streptonigrin is also seen in the response of DNA synthesis which is inhibited sharply in both A-T and normal cells using doses of up to 125 ng/ml, although the effect was less pronounced in A-T cells. A greater amount of time was needed for recovery of DNA synthesis in normal cells compared with that of A-T cells. Finally, chromosomes from both A-T lymphocytes and fibroblasts show about a doubling of breakage rate following exposure to streptonigrin. The increased sensitivity of A-T cells to streptonigrin appears to be fairly comparable to the sensitivity to ionizing radiation, bleomycin, or neocarzinostatin and provides further evidence that perhaps A-T cells are deficient in some form of DNA strand repair.
D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002877:Chromosomes, Human / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D013308:Streptonigrin / Q000494:pharmacology*
D013308:Streptonigrin; D004247:DNA