DNA Strand Scission by Neocarzinostatin and its Relation to the Inhibition of Cell Cycle Traverse and DNA Synthesis

Abstract

The effect of neocarzinostatin (NCS) on the cell cycle traverse of BHK cells was examined with flow microfluorometry and [³H]-thymidine incorporation. At a low concentration (1μg/ml) of NCS a large number of cells were arrested at the G₂ phase. At a high concentration (10μg/ml) cell cycle traverse from the G₁ to the S phase and DNA synthesis in the middle S phase were inhibited.
Chain elongation, strand scission and repair of DNA were determined by alkaline sedimentation analysis. In the presence of 10μg/ml NCS, parental DNA was degraded to the size of the replication unit (1.1×10⁸dalton). DNA elongated at most to the size of the replication unit, before the parental DNA was degraded to the same size. DNA strand scission took place even at the low concentration of NCS that induced G₂ arrest. The DNA strand scission induced by 10μg/ml NCS was repaired only slightly by 5 h afer the removal of NCS.
A short exposure of cells to NCS was sufficient to cause the inhibition of DNA synthesis and cell cycle traverse, as well as DNA strand scission.