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Cell Cycle-dependent Heat Sensitization of Murine Granulocyte-Macrophage Progenitor Cells in Regenerating Marrow¹

First Department of Internal Medicine, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan

The response of murine granulocyte-macrophage progenitor cells to hyperthermia was examined using normal and regenerating marrow. Hyperthermic exposure was given in vitro at 41–44 °C for periods of up to 60 min, and the results were compared between the 2 groups. Although almost no difference in percentage of survival was observed between them at 41 °C, murine granulocyte-macrophage progenitor cells of regenerating marrow showed markedly increased thermal sensitivity at and above 42 °C in comparison with that of normal marrow. Hydroxyurea suicide experiments revealed that the proportion of in vitro colony-forming units in the DNA-synthetic phase of the cell cycle [S phase] was greatly increased in regenerating marrow [66 ± 4% (SD)] as compared with that in normal marrow [18 ± 8%].

These data indicate that heat sensitization of hemopoietic cells occurs because of cell cycle effects, when they apparently mean the relative proportion of cells in S phase.

¹ Supported in part by Grant-in-Aid for Scientific Research No. 57480407 from the Ministry of Education, Japan.

² To whom requests for reprints should be addressed.

Received 6/25/84. Revised 12/ 4/84. Accepted 12/27/84.