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Studies on Unbalanced Growth in Synchronized HeLa Cells¹

Division of Biophysics, Sloan-Kettering Institute for Cancer Research, and Cornell University Graduate School of Medical Sciences, Cornell University Medical College, New York, New York 10021

Unbalanced growth leading to a loss of colony-forming ability is induced by exposing mitotically synchronized HeLa cells to inhibitors of DNA synthesis. A sharply reduced cell survival (colony-forming ability) is observed following exposure of cells in the G1-S transition phase to 1-ß-D-arabinofuranosylcytosine or hydroxyurea for a period longer than 6–8 hr, a period corresponding to about the duration of the DNA synthetic phase (S) in HeLa cells. A decrease in cell survival occurs when the cells in mitosis are exposed to the inhibitors of DNA synthesis for a period longer than 16 hr, a period corresponding to about the duration of the G1 and the S phases. Thus, it is concluded that the minimum time period needed for the induction of unbalanced growth leading to a loss of cell viability following exposure of HeLa cells to an inhibitor of DNA synthesis would be equal to the duration of DNA synthesis.

The use of cycloheximide, an inhibitor of protein synthesis, reverses the lethal effect of the inhibition of DNA synthesis. This finding indicates that the synthesis of protein may be one of the requisite steps in the induction of the unbalanced growth syndrome.

¹ This work was aided by grants from the National Cancer Institute (CA 08748) and the Atomic Energy Commission (AT (30-1)-910).

Received 5/23/68. Accepted 8/26/68.