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Cell Cycle-specific Enhancement of Type C Virus Activation by Sodium n-Butyrate¹

Biological Carcinogenesis Program, Frederick Cancer Research Center, Frederick, Maryland 21701

The effect of sodium n-butyrate on chemical induction of xenotropic virus from synchronized Kirsten sarcoma virus-transformed BALB mouse cells was examined. When added during the last part of the G₁ phase, n-butyrate produced a large increase in cycloheximide induction during S phase. Under similar conditions, activation by 5-iododeoxyuridine was inhibited. When added with cycloheximide during the S phase, n-butyrate inhibited activation of virus. Studies with synchronized cultures showed that n-butyrate delayed the onset of DNA synthesis, characteristic of the S phase, and inhibited histone deacetylation in log-phase cells. The effects produced by n-butyrate could, therefore, be the result of lengthening the G₁ phase of the cell cycle or a modification of histones affecting transcription during virus activation.

¹ This work was supported by Contract NO-1-CO-75380 with the National Cancer Institute, NIH, Bethesda, Md. 20205.

² To whom requests for reprints should be addressed.

Received 4/28/80. Accepted 7/24/80.

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