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Hydroxyurea: Effects on Chinese Hamster Cells Grown in Culture¹

Division of Biological and Medical Research, Argonne National Laboratory, Argonne, Illinois

Hydroxyurea has both inhibitory and cytotoxic action on Chinese hamster cells grown in vitro. During short exposures, the lethal action is selective for cells in DNA synthesis (S cells) only. The inhibitory effect prevents incorporation of tritiated thymidine into DNA while RNA and protein synthesis continue essentially without modification, at least until near the end of the cycle. S cells, destined to die, fail to divide after exposure to hydroxyurea, but resynthesize DNA after the drug is removed, enlarge to 3–4 times the normal volume during the next 20–30 hr, and then lyse. Cells at stages of the cell cycle, other than S, progress normally until the time DNA synthesis should have begun. A condition of unbalanced growth then ensues, which cells tolerate quite well for some hours, and from which they recover when relieved. They cannot remain viable in this condition indefinitely, however, and die after being inhibited for about 8–10 hr (i.e., about the time the next division should have occurred).

The lethal and inhibitory actions of the drug make it a useful synchronizing agent in asynchronous populations, even though the length of the S period may be slightly reduced thereafter. Furthermore, although inhibited cells are more sensitive to X-rays in the presence of the drug, they recover normal X-ray responses within a short time after the drug is removed.

¹ Work supported by the United States Atomic Energy Commission.

Received 6/10/66. Accepted 9/ 1/66.

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