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Survival Responses of Dividing and Nondividing Mammalian Cells after Treatment with Hydroxyurea, Arabinosylcytosine, or Adriamycin¹

Division of Cell Biology, Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, Texas 77550

One-hr treatments of Chinese hamster ovary cells in plateau phase with the cell cycle-active drugs hydroxyurea or cytosine arabinoside produced no effects on survival. Plateau-phase cells treated with adriamycin (1 to 10 µg/ml for 1 hr) exhibited a biphasic survival curve similar to that for exponentially growing cells. The most sensitive population of exponentially growing cells had a D₀ = 0.2 µg/ml for 1 hr, and a D₀ = 9.4 µg/ml for 1 hr in the more resistant population of the biphasic survival curve. The survival curve for the plateau phase cells had D₀ = 0.7 µg/ml for 1 hr and 6.4 µg/ml for 1 hr for the sensitive and resistant parts of the curve, respectively. Although the plateau cells were less sensitive than exponentially growing cells, the survival fraction was still reduced to 4% by 10 µg/ml for 1 hr. Therefore, these data suggest that adriamycin may be an effective agent for use on slowly growing solid tumors which contain large fractions of nondividing cells. In addition, the in vitro results of adriamycin on nondividing cells may be predictive of side effects on normal stem cell compartments in the bone marrow and small intestine.

¹ Supported in part by Grant 1 RO1 CA15397-01, National Cancer Institute, NIH, USPHS.

Received 1/29/74. Accepted 3/25/74.