Cell cycle-dependent heat sensitization of murine granulocyte-macrophage progenitor cells in regenerating marrow

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 degrees 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 degrees C, murine granulocyte-macrophage progenitor cells of regenerating marrow showed markedly increased thermal sensitivity at and above 42 degrees 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.