Inhibition of DNA and RNA Synthesis in Rat Liver Nuclei by Oncogenic and Non-oncogenic β-Blockers

Abstract

The β-blocker DL-1-(2-nitro-3-methylphenoxy)-3- tert-butylaminopropan-2-ol (ZAMI 1305), hepatocarcinogenic to the female rat, and the non-oncogenic β-blockers DL-1-(2-nitro-5-methylphenoxy)-3- tert-butylaminopropan-2-ol (ZAMI 1327), DL-propranolol, and DL-atenolol were studied for their capacity to interfere with hepatic DNA and RNA synthesis. These moieties inhibit DNA and RNA synthesis, in a dose-dependent fashion, when added in vitro to nuclei isolated from the liver of male or female rats. The inhibition is due to a decrease of the initial rate of synthesis and of the total amount of labeled precursor incorporated into the growing chains. When administered in vivo both the oncogenic ZAMI 1305 and its non-oncogenic isomer ZAMI 1327 inhibit hepatic DNA and RNA synthesis in female rats, as evaluated by the determination of nucleic acids synthesis in liver nuclei isolated from female rats 5 and 15 min after the injection of the drug. No influence on hepatic DNA and RNA synthesis is observed when the molecules are administered to male rats. The in vivo administration of DL-propranolol causes an increase of hepatic DNA and RNA synthesis in male rats, while it is uneffective in female rats.