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Selective Toxicity Induced by Picolinic Acid in Simian Virus 40-transformed Cells in Tissue Culture¹

Nuclear Medicine Laboratory, VA Hospital and St. Louis University, St. Louis, Missouri 63125 [J. A. F-P.], and Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20014 [G. S. J.]

When cultured normal and SV40-transformed normal rat kidney and BALB/3T3 cells were exposed to picolinic acid, cell proliferation ceases. Most of the normal cells remained in a quiescent G₁(G₀) state and viable for prolonged periods of time. In contrast, SV40-transformed cells progressed to the S and G₂ phases of the cell cycle and remained viable only up to 90 to 120 hr. Then, most of the cells began to die. However, a very small fraction of the cell population (approximately 0.01%) developed into variants resistant to picolinic acid. Prevention of development of variants, and therefore destruction of all transformed cells, was obtained by addition of glycerol to picolinic acid-treated cells. Untransformed cells were unaffected by the same treatment. These results suggest that differential tumor toxicity should be feasible.

¹ A portion of this study was supported by the Veterans Administration, MRISS 657/2620-01.

² Supported during part of this work by an Individual National Research Service Award 1F32 CA05166-01 from the National Cancer Institute. To whom requests for reprints should be addressed, at Nuclear Medicine Laboratory (115JC), Veterans Administration Hospital, Saint Louis University, St. Louis, Mo. 63125.

Received 4/22/77. Accepted 8/25/77.

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