Comparison of the Action of ³H-Thymidine and Hydroxyurea on Testosterone-treated Hemopoietic Stem Cells

The treatment of mice with a single, subcutaneous injection of either testosterone propionate or of 5β-dihydrotestosterone results in an increase in the sensitivity of spleen colony-forming cells (CFU-S) to the cytocidal action of high specific activity ³H-TdR. The effect is still present 24 hr after treatment. By 1 hr after exposure in vitro to 2.4 x 10^-8M testosterone hydrogen succinate (THS), CFU-S from mouse bone marrow similarly become more sensitive to ³H-TdR. Sensitivity to the cytotoxic action of 10^-3M hydroxyurea (HU) also increases. Compared with ³H-TdR sensitivity, however, there is a delay in the onset of sensitivity to HU. The lag is shortened if HU is added 1 hr after the addition of THS. The increased sensitivity of CFU-S to HU is prevented by deoxyribonucleoside, i.e., unlabeled thymidine, and the change during the first hour in ³H-TdR sensitivity is unaltered by the presence of HU. From these data, it is suggested that CFU-S from normal bone marrow contain precursors for DNA synthesis, e.g., deoxyribonucleotides. On the assumption that the action of HU is to inhibit the formation of deoxyribonucleotides from ribonucleotides, the delay in the onset of action of HU may depend on the exhaustion of such pools. It is postulated that CFU-S responding to THS are held up in a stage of the cell cycle close to the G₁-S boundary.