Effect of inhibition of DNA synthesis on histone synthesis, turnover, and deposition in the rat testis.

In testicular seminiferous epithelial cells (SEC) of normal and hypophysectomized rats, 1-beta-D-arabinofuranosylcytosine and hydroxyurea (at concentrations which inhibited DNA synthesis nearly completely) inhibited histone synthesis only partially, and to a different extent for each histone fraction. In the presence of the inhibitors, the extent of synthesis relative to the corresponding control was TH1-x greater than H1 greater than TH2B-x = X2 = H2A greater than H2B = H3 greater than H4, in which synthesis of the H4 fraction was about 50% of control and that of TH1-x was 90-95% of control. The extent of inhibition of synthesis of each histone fraction was similar after hypophysectomy and, therefore, the changing of the relative populations of heterogeneous cells in the SEC did not influence the relative effects of the inhibitors of DNA synthesis on the synthesis of the various histone fractions. After [3H]leucine injection, the molar proportions of labeled histones relative to H4 decreased markedly between 1.5 h and 6-15 days; this finding indicated that there was rapid removal of histones compared to the H4 fraction during this period. When [14C]thymidine was injected 24 h prior to hydroxyurea treatment and [3H]leucine injection, the ratios of specific activities of histone H4 to DNA did not change significantly over an 11-day period. It appears that newly synthesized histone H4 and other somatic histones are associated with existing DNA in the presence of DNA inhibitors.