In vitro inhibition of rat liver DNA polymerases α and β by β-blockers

Abstract

The activity of DNA polymerases α and β, isolated from regenerating rat liver, is inhibited, in a dose-dependent fashion, by the oncogenic β-blocker DL-I-(2-nitro-3-methyl-phenoxy) - 3-tert-butylamino-propan-2-ol (ZAM[ 1305) and by non-oncogenic β-blockers DL-l-(2-nitro-5-methyl-phenoxy-3-tert-butylamino-propan-2-ol (ZAMI 1327) and DL-propranolol. The inhibition is due to a reversible interaction of the g-blockers with the two DNA polymerases. The interaction does not involve the template-DNA-binding site or the deoxynucleotide-binding site of the enzyme molecule. The degree of inhibition appears to be related to the hydrophobicity of the aromatic moiety and to the length and/or hydrophilicity of the aliphatic chain of the β-blocker molecule. These results may explain the transient in vivo inhibition of hepatic DNA synthesis observed in female rats treated with ZAMI 1305 or ZAMI 1327.