DNA STRAND SCISSION BY NEOCARZINOSTATIN AND ITS RELATION TO THE INHIBITION OF CELL-CYCLE TRAVERSE AND DNA-SYNTHESIS

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 (1 µg/ml) of NCS a large number of cells were arrested at the G2 phase. At a high concentration (10 µg/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 10 µg/ml NCS, parental DNA was degraded to the size of the replication unit (1.1 x 108 dalton). 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 10 µg/ml NCS was repaired only slightly by 5 h after 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. © 1979, Japan Society for Cell Biology. All rights reserved.