Histone and DNA synthesis in differentiating and rapidly proliferating cells in vivo and in vitro

The dependence of histone synthesis upon concurrent DNA synthesis has been studied in rat spermatogenic and brain tumor (RT489) cells, both in vivo and in vitro. The uptake of [3H]amino acids into histone was determined with and without inhibiting DNA synthesis with hydroxyurea (HU). HU reduced [14C]thymidine incorporation into DNA to less than 5% of control values in all cases without affecting the levels of total cellular protein synthesis, confirming the specificity of HU for inhibiting DNA synthesis. RT489 cells, grown either in culture or as a solid tumor, show no detectable histone synthesis when the concentrations of HU are sufficiently high. In the testis, no inhibition of synthesis of histones occurring during the meiotic prophase is observed in vivo or in vitro. These results provide further support for the model that a high degree of coupling of histone and DNA synthesis may occur only in proliferating, non-differentiating cell types and that both types of regulation can be observed both in in vivo and in vitro systems.