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.

This content is only available as a PDF.