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In Vivo Cell Cycle Synchronization of the Murine Sarcoma 180 Tumor following Alternating Periods of Hydroxyurea Blockade and Release¹

Department of Medicine B, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14263

The durations of the cell cycle intervals of the murine Sarcoma 180 tumor were determined by computer analysis of the fraction-labeled mitosis curve following tritiated thymidine administration. This tumor has a usual total cell cycle duration of 19.6 hr, a DNA synthetic time of 8.3 hr, and a growth fraction of 1. Approximately 38% of cells are in S phase at one time. Hydroxyurea (HU) infusions (i.v.) at 1.17 mg/hr into tumor-bearing mice rapidly inhibit tumor DNA synthesis. Following a 5-hr HU infusion, 58% of all tumor cells are in S phase, and maximal tumor mitotic rates after release of the HU blockade are double control rates.

HU was infused for 5 hr, followed by 7 hr of Ringer's solution, and then another 5 hr of HU. Following this 2-cycle blockade, 70% of tumor cells are in S phase, predominantly in early S phase and at the G₁-S junction. After release, peak mitotic rates are 2.5 times control. The duration of the intermitotic time of the tumor following HU infusion is less than the total cell cycle time of control tumor. Cycles of HU infusion and release, timed according to the predetermined duration of the cell cycle intervals, will synchronize significant increments of S phase or mitotic cells of the Sarcoma 180 tumor during predictable periods of time.

¹ Supported by the National Cancer Institute, United States Public Health Service Grant CA-19097.

² To whom requests for reprints should be addressed, at Roswell Park Memorial Institute, Department of Health, State of New York, 666 Elm Street, Buffalo, N.Y. 14263.

Received 2/27/78. Accepted 8/ 6/79.

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