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Hydroxyurea has a differential lethal effect on cultured Chinesehamster cells that are at different stages in their cell cycle. Cells synthesizing DNA at the time of exposure to the drug are lethally damaged. Cells in the phase of growth preceding DNA synthesis (G(1)) survive but are prevented from beginning DNA synthesis. Cells in the phase after DNA synthesis (G(2)) survive and appear to progress until just before the beginning of the next period of DNA synthesis. This differential lethal and inhibitory effect of hydroxyurea may be useful for synchronizing asynchronous cell populations and explaining effects of the drug in human therapy.

Populations of Chinese hamster cells, synchronized by selecting for cells at or close to division, were exposed to 250 kvp x-rays and to ultraviolet light at different stages of the cell cycle and colony-forming ability examined thereafter. These cells were found to be most resistant to x-rays during the latter part of the DNA synthetic period (S) and to be about equally sensitive before (G(1)) and after (G(2)) this period. Multitarget type curves of the same slope (D(o) approximately 200 rad) only approximately fitted the survival data at different stages in the cycle. The changes in response were primarily due to variations in the shoulders (or extrapolation numbers) of the curves however. The response to ultraviolet light differed from that to x-rays. Resistance was greatest in G(2) and changes in both shoulder and slope of the survival curves occurred throughout the cell cycle. The x-ray and ultraviolet responses for component stages of the cell cycle were respectively compounded into expected survival data for a log phase asynchronous population of hamster cells and found to agree well with direct experiment.

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