Mazzocchi C, Presta M, Ziliani S, Romano A, Ragnotti G
Chem Biol Interact. 1984 Jun;50(1):77-86. doi: 10.1016/0009-2797(84)90133-9.
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.
在体外和体内测试了致癌性β受体阻滞剂1-(2-硝基-3-甲基苯氧基)-3-叔丁基氨基丙-2-醇（ZAMI 1305）的D-异构体和DL-外消旋体以及非致癌性β受体阻滞剂普萘洛尔对核酸合成和DNA完整性的影响。将D-ZAMI 1305和DL-ZAMI 1305体外添加到从大鼠肝脏分离的细胞核中时，通过碱性蔗糖梯度分析评估，二者均以相似的剂量依赖性方式抑制DNA和RNA合成以及DNA片段化。D-ZAMI 1305和DL-ZAMI 1305对再生大鼠肝脏的DNA聚合酶α和β的活性也有相似程度的抑制作用。当对雌性大鼠进行体内给药时，D-ZAMI 1305和DL-ZAMI 1305均导致肝脏DNA呈剂量依赖性片段化。非致癌性β受体阻滞剂普萘洛尔的D-异构体和DL-外消旋体在体外添加到分离的肝细胞核中时会抑制DNA和RNA合成并导致DNA片段化，而在体内给药时则无此作用。
