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Phase Specificity of 5-Azacytidine against Mammalian Cells in Tissue Culture¹

Cancer Research, The Upjohn Company, Kalamazoo, Michigan 49001

5-Azacytidine (1 to 5 µg/ml) significantly inhibited mitosis of L1210 cells in culture only after 2 hr of incubation. The inhibition of mitosis was correlated to the inhibition of DNA synthesis.

With asynchronous DON and L1210 cells, the cell-kill (inhibition of proliferative capacity) reached a saturation value at high doses of the drug. Any further increase in drug concentration did not result in a corresponding increase in percentage of cell-kill. This indicated that 5-azacytidine kills cells in certain phases of the cell cycle. With synchronous DON cells, it was shown that the drug was lethal predominantly in the S phase.

5-Azacytidine caused considerable chromosome damage when L1210 cells in culture were exposed to the drug at 5 µg/ml for 2 hr at 37°.

¹ This investigation was supported in part by Contract PH43-68-1023 with Chemotherapy, National Cancer Institute, NIH, Bethesda, Md.

Received 3/30/70. Accepted 7/21/70.

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