Stimulation of DNA synthesis in primary cultures of adult rat hepatocytes by sodium butyrate.

Replicative DNA synthesis in primary cultures of adult rat hepatocytes is increased by the addition of the histone deacetylase inhibitors, propionate or butyrate. DNA synthesis was increased by the addition of 0.5 or 1.0 mM butyrate; in contrast 5.0 mM butyrate inhibited replicative DNA synthesis. Replicative DNA synthesis was increased only when low levels of butyrate were added as the hepatocytes entered the S phase. The observed apparent increase in replicative DNA synthesis was real, and not owing to changes in the specific activity of the dTTP precursor pool. The effects of butyrate and propionate on DNA synthesis appear to be related to their effects on histone acetylation.