The effects of alkylating agents and DNA ase on nucleic acid synthesis in rat-liver nuclei in vitro

Abstract

Adult female rat-liver nuclei have been treated with nitrogen mustard (HN 2), methylene dimethane sulphonate (MDMS) and bovine pancreatic DNAase I. DNA synthesis and RNA synthesis in this system have been assayed using the methods of labelled TTP and UTP uptake. The results indicate that low concentrations of MDMS and HN 2 stimulate RNA synthesis and that this effect may be simulated by treatment with low levels of DNAase I. However, a similar parallelism between the actions of higher concentrations of MDMS and DNAase does not appear to exist since at such concentrations MDMS does not affect DNA synthesis whereas DNAase stimulates DNA synthesis. At these levels, however, both MDMS and DNAase inhibit RNA synthesis. It is suggested that low levels of MDMS and HN 2 affect RNA synthesis in rat-liver nuclei by inducing breakage of the DNA template, whereas higher levels of these agents could inhibit RNA synthesis in the nuclei by a different mechanism.