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Age Responses of Cultured Mammalian Cells to Cytotoxic Drugs¹

Division of Radiation Biology, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110

A number of cytotoxic drugs (mitotic poisons, chemical mutagens, bifunctional alkylating agents, inhibitors of DNA, RNA, or protein synthesis, for a total of 18 agents) have been tested for differences in their lethal effects through the generation cycle of HeLa and Chinese hamster cells in culture. The patterns of age response of cells to each group of agents show some features in common: mitotic poisons, chemical mutagens, and inhibitors of DNA synthesis appear to be most effective on cells in S phase, alkylating agents in M and G₁, and inhibitors of protein synthesis at the G₁/S transition, whereas inhibitors of RNA synthesis elicit an X-ray-like age response, i.e., show grestest activity on cells in M and at the G₁/S transition. Further differences in lethal action have been defined by microscopic observations of the treated cells; these permit additional distinctions to be made between groups of agents. In the case of asynchronous cell populations, all the agents but 3 give rise to sigmoidal concentration-survival curves (an initial shoulder followed by an exponential decline). The exceptions are nitrogen mustard, which elicits an exponential curve, and hydroxyurea and pederine, which give rise to exponential curves followed by a plateau at about 45% survival level.

¹ This investigation was supported by USPHS Research Grants CA-04483 and CA-10435 from the National Cancer Institute.

Received 10/24/69. Accepted 1/ 7/70.