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Lethal and Sublethal Effects of Hydroxyurea in Relation to Drug Concentration and Duration of Drug Exposure in Sarcoma 180 In Vitro

Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20014

The lethal and sublethal effects of hydroxyurea were studied in Sarcoma 180 in vitro in relation to drug concentration and drug exposure duration using cloning methods, radioautography, and flow microfluorometry. It was shown that postperturbation changes in radioautographic labeling intensity reflected real changes in the rate of DNA synthesis in individual cells. The data suggest that both the lethal and sublethal effects of hydroxyurea are dependent on the rate of DNA synthesis. These findings have important implications for the interpretation of DNA content distributions under perturbation conditions and for the development of drug treatment regimens that are based on cell kinetics.

¹ To whom requests for reprints should be addressed, at National Cancer Institute, Bldg. 10, Room 6N113, Bethesda, Md. 20014.

Received 11/ 5/76. Accepted 5/13/77.