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Action of Daunomycin on the Nucleic Acid Metabolism and Viability of HeLa Cells¹

Division of Biophysics, Sloan-Kettering Institute for Cancer Research, New York, New York 10021

Daunomycin, an antibiotic, promptly inhibits DNA and RNA synthesis and stops cell division in HeLa cells. The inhibitory action of the antibiotic is thought to result from the ability to bind to DNA. Thus, the interaction of the antibiotic with DNA can be demonstrated by a DNA concentration effect on the inhibition of in vitro DNA synthesis using DNA polymerase from Escherichia coli. Some of the in vivo enzymatic activities related to DNA synthesis are not reduced. In fact, thymidine kinase and deoxycytidine monophosphate deaminase activities are higher than those of control cells at 6 hr after exposure of cells to the antibiotic. DNA polymerase activity is not significantly reduced. Studies on the lethal effects of daunomycin in terms of colony formation during the division cycle show that the antibiotic is most toxic during the DNA synthetic phase (S) and least during the pre-DNA synthetic phase (G-1). The significance of these findings is discussed.

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

Received 4/ 3/68. Accepted 8/ 8/68.