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Differential Cytotoxicity between Transformed and Normal Human Cells with Combinations of Aminonucleoside and Hydroxyurea

Laboratory of Molecular Pharmacology, Division of Cancer Treatment, NIH, National Cancer Institute, Bethesda, Maryland 20014

Normal human WI-38 cells can be protected from killing by hydroxyurea if proliferation is arrested during drug treatment. This protection was demonstrated both in cells arrested by density-dependent inhibition and by 3'-amino-3'-deoxy-N⁶,N⁶-dimethyladenosine (puromycin aminonucleoside). In contrast, VA-13 cells (a simian virus 40-transformed clone of WI-38) were not arrested under these conditions, and continued to be sensitive to hydroxyurea. These results suggest that a search for agents that selectively and reversibly inhibit normal cycling human cells might lead to an enhancement of differential tumor toxicity.

Received 11/22/76. Accepted 4/ 7/77.