Neocarzinostatin induction of DNA repair synthesis in HeLa cells and isolated nuclei.
The antitumor antibiotic neocarzinostatin that causes DNA strand breaks in vivo and in vitro is shown to induce DNA repair synthesis in HeLa S3 cells. In the repair assay, the parental DNA was prelabeled with 32P and a density label (bromodeoxyuridine) was introduced into the new synthesized DNA. Quantitation of the repair synthesis as measured by the incorporation of [3H]thymidine into the light parental DNA at varying doses of the drug indicate that there is a significant repair response at low levels of the drug (0.2--0.5 microgram/ml) which cause DNA strand breakage and inhibition of DNA synthesis. In isolated HeLa nuclei neocarzinostatin stimulates the incorporation of dTMP many-fold. This enhancement of dTMP incorporation, which requires the presence of a sulfhydryl agent, is a consequence of the drug-induced DNA strand breakage and is in the parental DNA. These results suggest that an intact cell membrane is not required for DNA strand breakage and its subsequent repair.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells / Q000187:drug effects; D008623:Mercaptoethanol / Q000494:pharmacology; D013268:Stimulation, Chemical; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D008623:Mercaptoethanol; D009353:Zinostatin