Decreased Sensitivity to Hydroxyurea and to [3H]Thymidine Suicide In the Middle of the S Phase

Abstract
Pluripotent hemopoietic stem cells (CFU [colony forming units]) move synchronously through the cell cycle in hydroxyurea-treated mice in a cohort 1-2 h broad. At 10-15 h after hydroxyurea treatment they pass through the S phase. DNA synthesis appears depressed 5-10 times when the cells are in the middle part of the S phase but does not seem completely interrupted. High concentrations of [3H]thymidine must be used for suicide to achieve lethality for the cells with depressed DNA synthesis. When DNA synthesis is depressed, the sensitivity of the cells to hydroxyurea also decreases. This may lead to a significant underestimation of the S phase fraction by the hydroxyurea method, because CFU with a low DNA synthesis rate are resistant to hydroxyurea although being in the S phase.