Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells.

TLDR

Differences in inhibition patterns may arise from drug biotransformation or preferential binding to chromosomal DNA in intact cells. The study investigated adriamycin’s effects on DNA, RNA, and protein synthesis in cell‑free systems and intact cells. Adriamycin inhibited DNA polymerase more than RNA polymerase in cell‑free systems, with inhibition reduced by excess DNA template; in isolated nuclei it more strongly blocked DNA synthesis, whereas in intact cells it inhibited DNA and RNA synthesis to similar extents, with RNA inhibition exceeding that in cell‑free systems, and it suppressed protein synthesis only in cell‑free preparations.

Abstract

The effect of adriamycin on DNA, RNA, and protein synthesis was investigated in cell-free systems and intact cells. In studies with purified mammalian cell enzymes, adriamycin produced a greater inhibition of DNA-dependent DNA polymerase than of RNA polymerase. The extent of inhibition of both these enzymes was decreased by increasing the concentration of the DNA template in the reaction mixture. In studies with isolated nuclei, adriamycin was also a more potent inhibitor of DNA synthesis than RNA synthesis. However, with intact cells, adriamycin inhibited both DNA and RNA synthesis to about the same extent. The inhibition produced by adriamycin on RNA synthesis in intact cells was greater than that observed in the cell-free systems. Adriamycin inhibited protein synthesis in a cell-free system consisting of polyribosomes, transfer RNA, and enzymes but did not inhibit protein synthesis in intact cells. These differences in the pattern of inhibition may be due to biotransformation of the drug and/or preferential binding to chromosomal DNA in the intact cell.