喜树碱(CPT)与10—羟基喜树碱(HCPT)的抗肿瘤活性与毒性比较

AN EXPERIMENTAL EVALUATION OF THE ANTITUMOR ACTIVITY AND TOXICITY OF CAMPTOTHECIN (CPT) VERSUS 10-HYDROXYCAM-PTOTHECIN (HCPT)

给小鼠一次腹腔注射(ip),CPT的LD_(50)为65.7±11.3mg/kg,HCPT为149.6±29.7mg/kg。“等毒性”剂量的HCPT对腹水型肝癌(HepA)、艾氏腹水癌(EAC)及肉瘤180(S_(180))小鼠的抗癌作用强于CPT。二药均能抑制HepA细胞DNA、RNA合成及膜的核苷转运。CPT及HCPT对HepA小鼠的治疗比分别为2.5和25,HePT对小鼠的骨髓毒性明显低于CPT。

The single ip LD 50 in mice was determined to be 65.7± 1.3mg/kg for CPT and 149.6±29.7 mg/kg for HCPT. The antitumor activity of HCPT was higher than that of CPT at the equi-toxic dose on the mice bearing ascites hepatorna,Ehrlich ascites carcinoma and ascites sarcoma 180. Both brugs could inhibit the syntheses of DNA and RNA. and inhibit transportation of thymidine and uridine into the hepatorna ascites cells in vitro. The therapeutic ratio of HCPT and CPT was 25 and 2.5 in mice bearing ascites hepatorna, respectively. HCPT exhibited less toxicity than CPT on the bone marrow stem cells in normal mice. Our results showed that HCPT pgossesses higher antitumor activity and less toxi City as compared with CPT.