Giant cell formation in cultured L5178Y lymphoblasts induced by hydroxyurea treatment

The conditions leading to hydroxyurea-induced abnormal cell enlargement (giant cell formation) were studied in L5178Y lymphoblasts in the culture. Exposure for only 1 hour to a concentration of 1 mM hydroxyurea (HU) was sufficient to produce an abnormal enlargement of about 25 percent of the cells. The maximal proportion of giant cells reached the value of about 50 percent after treatment with 1 mM HU for 5 hours and was not changed by a further prolongation of exposure time and/or by increasing the concentration of HU to 10 mM. Comparison of cell populations with various proportions of giant cells as regards their ability to reproduce, DNA synthesis and persistence in the culture suggested that at least some part of giant cells lost the ability to divide, their DNA synthesis was markedly suppressed or retarded and more than 50 percent of them disappeared earlier than 48 hours after the termination of HU exposure. It is concluded that at least at certain HU concentrations and in suitable stage of target cells the response of cells to short HU treatment can resemble that produced by X-rays or other DNA damaging agents.