Cell kill kinetics with hydroxyurea

The effects of various concentrations of hydroxyurea (HU) on a human lymphoid cell line in exponential growth phase have been studied using a combination of methods, including determination of the total and viable cell counts; the cells relative DNA content, measured in a flow microfluorimeter after staining with a fluorescent Feulgen technique; the mitotic index; and the percentage of cells incorporating thymidine-3H (TdR-3H) during brief and continuous exposure to the isotope both in the presence and absence of colcemid. A significant redistribution of the cells in the various phases of the cell cycle occurred during the first 24 hr of continuous treatment with 10(-3) M and 10(-2) M HU as follows: (1) division of cells in G2; (2) depletion of mid and late S phase cells due to early cell death; (3) movement of most G1 cells at a normal rate into early S phase where they accumulate; and (4) arrest of the remaining cells in G1, which represented the surviving population after treatment for 96 hr or longer. After removal of the drug, the cell fraction blocked in early S phase progressed semisynchronously through S, but many of the cells were unable to complete division. Their capacity to recover depended on the drug concentration and duration of exposure, but in general the cellular injury caused by HU was more reversible than that caused by "equivalent" concentrations of arabinosylcytosine.