Optical isomers of the hepatocarcinogenic beta-blocker ZAMI 1305: influence on nucleic acids synthesis and DNA integrity.

The influence on nucleic acids synthesis and DNA integrity of the D-isomer and of the DL-racemic form of the oncogenic beta-blocker 1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305) and of the non-oncogenic beta-blocker propranolol was tested in vitro and in vivo. Both D- and DL-ZAMI 1305, when added in vitro to nuclei isolated from rat liver, cause inhibition of DNA and RNA synthesis and DNA fragmentation, as evaluated by alkaline sucrose gradient analysis, in a similar dose-dependent fashion. D- and DL-ZAMI 1305 also inhibit to a similar extent the activity of DNA polymerase alpha and beta from regenerating rat liver. When administered in vivo to female rats both D and DL-ZAMI 1305 cause a dose-dependent fragmentation of liver DNA. The D-isomer and DL-racemic form of the non-oncogenic beta-blocker propranolol inhibit DNA and RNA synthesis and cause DNA fragmentation when added in vitro to isolated liver nuclei, being instead without effect when administered in vivo.