The addition of fractionated heterologous histone to the incubation medium reduced DNA and RNA synthesis in intact 6C3HED ascites tumor cells of mice and in spleen cells from nontumor-bearing mice. Acid-soluble phosphorus and acid-soluble nucleotide phosphorus specific activities were not affected by added histone, but electron microscopy revealed cellular changes which suggested some loss of viability.
Arginine-rich and intermediate histone fractions inhibited DNA synthesis to a greater degree than did very lysine-rich histone; moreover, when whole cells were used, there was greater inhibition of DNA than RNA synthesis by all histone fractions. DNA synthesis in spleen cells showed significantly more reduction than such synthesis in ascites tumor cells; arginine-rich histone caused a reduction of DNA synthesis to 53.1% of control in tumor cells and to 11% of control in spleen cells.
The various histone fractions, labeled with 14C, penetrated intact cells to differing degrees, as demonstrated by autoradiography and by comparison of specific activity in the incubation medium and in the acid-extracted cell homogenate. The quantity of each fraction penetrating both cell types was similar, and this quantity did not correlate well with the extent of inhibition of nucleic acid synthesis.
These findings suggest that ascites tumor cells are more resistant to inhibition of nucleic acid synthesis by added histones than are normal spleen cells; this difference may depend upon factors other than the amount of histone entering the cell.
This investigation was supported in part by Public Health Research Grants No. CA-08344-2, CA-08832, CA-05862, CA-05158, and CA-08101 from the National Cancer Institute and Public Health Service Training Grant No. 5-Tol-HD 00053-07 (A.S.L.).