DNA damage and repair in relation to cell killing in neocarzinostatin-treated HeLa cells.
To elucidate the mechanism of the cell killing activity of neocarzinostatin on mammalian cells, the drug-induced damage of DNA and its repair were examined. Very low doses of neocarzinostatin, at which high survival of cells was observed, clearly produced single-strand breaks of DNA and decomposition of the 'DNA complex', but these damages appeared to be repaired almost completely. At higher doses of neocarzinostatin, single-strand breaks were repaired to a considerable extent while double-strand breaks seemed not to be repaired. The number of non-repairable single-strand breaks was about twice that of double-strand breaks. This implies that single-strand breaks are repaired except for those constituting double-strand breaks. Although at low levels of neocarzinostatin repair of double-strand breaks may occur, the correlation existing between the colony-forming ability of cells treated with neocarzinostatin and non-repairable DNA breakage suggests that production of a small number of critical non-repairable double-strand breaks per cell may be responsible for the cell killing activity of the drug.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002499:Centrifugation, Density Gradient; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D009353:Zinostatin