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The Relationship between Polyamine Accumulation and DNA Replication in Synchronized Chinese Hamster Ovary Cells after Heat Shock¹

University of Arizona College of Medicine, Departments of Pharmacology and Radiology [D. H. R.]/Division of Radiation Oncology [E. W. G.], Tucson, Arizona 85724

The relationship of polyamine accumulation and semiconservative DNA replication was studied in synchronous Chinese hamster ovary cultures, progressing through the cell cycle either normally at 37° or after hyperthermic exposure (43° for 1 hr) during G₁ or S phase. In control cultures, intracellular polyamine levels decreased as cells divided and then reaccumulated as cells exited G₁ and proceeded through the S and G₂ phases. Immediately after cultures were exposed to 43° heat for 1 hr in G₁ phase, intracellular levels of spermidine and spermine were reduced compared to controls. Coordinate with the depletion of the intracellular levels of these polyamines following exposure at 43°, extracellular levels of spermidine and spermine were increased. The ratio of intracellular to extracellular amounts of both these polyamines changed from 1 to 1.5 to approximately 0.2 to 0.3 after hyperthermic exposure. These cultures exposed to 43° heat during G₁ initially showed depressed levels of replicated DNA, but near-control rates of DNA replication were attained in a temporally related manner with the reaccumulation of intracellular spermidine and spermine levels. When cultures were exposed to 43° heat in S phase, intracellular amounts of spermidine and spermine were again reduced, and increased extracellular levels of these polyamines were observed. In these S-phase-treated cultures, cells were able to continue replicating their DNA but at a much reduced rate compared to controls. These results and others show that: (a) exposure of cells at 43° causes a depletion of intracellular levels of spermidine and spermine, suggesting that an immediate aspect of thermal damage is a membrane defect that markedly affects the transport of these molecules across cell membranes; (b) exposure of either G₁- or S-phase cultures to 43° heat caused a depression of bulk DNA-synthetic rates resulting in a prolongation of S phase, and (c) the intracellular reaccumulation of spermidine and spermine following exposure of G₁ cells to a 43° heat shock is temporally related to the recovery of near-normal DNA synthetic rates in these cells.

¹ This work was supported by Grant IN-110 from the American Cancer Society and by USPHS Grants CA-18273, CA-14783, CA-17343, and CA-17094.

² Recipient of Research Career Development Award CA-00072 from the National Cancer Institute.

Received 12/29/75. Accepted 11/ 5/76.