阿霉素和安吖啶及其DNA复合物对小鼠的毒性和抗肿瘤作用

STUDY ON THE TOXICITY AND ANTITUMOR ACTIVITY OF ADRIAMYCIN-DNA AND AMSACRINE-DNA COMPLEXES IN MICE

研究了阿霉素(ADR)和安吖啶(AMSA)与小牛胸腺DNA结合成复合物的药理特性。ADR与DNA的结合强度约相当AMSA的100倍。ADR—DNA复合物比ADR本身毒性小(LD_(50)提高0.45倍)。经ip后在小鼠S180三种实验模型(皮下、腹腔、静脉接种瘤)抗肿瘤作用增强。ADR—DNA较ADR吸收缓慢且血药浓度高2.5倍,药时曲线下面积(AUC)高2.8倍。ip后8h,心、肝、肺、肾、小肠和瘤中药物浓度,ADR—DNA组高于ADR组。AMSA—DNA和AMSA的毒性、AUC及抗癌作用无明显区别。

We have compared in vitro binding of adriamycin(ADR) and amsacrine(AMSA) with DNA, the toxicity, and the antitumor activity of ADR-DNA and AMSA-DNA, after in- traperitoneal(ip) injection in mice. The binding of ADR with DNA is 100--fold higher than that of AMSA with DNA. The overall toxicity of ADR--DNA is singnificantly lower than that of ADR. ADR--DNA is more effective than ADR against three models of S180 sarcoma (by sc,ip and iv inocu- lation into mice). The peak levels of ADR--DNA and ADR were 265±24 ng·ml^(-1) versus 108±16 ng·ml^(-1)(P<0. 01). AUC 0～12 h were 1064±84 ng·h^(-1) ·ml^(-1) versus 382±27 ng·h^(-1)· ml^(-1) (P<0. 01). The levels of ADR in most of tissues and tumor after adminstration of ADR--DNA were higher than those after administration of ADR. Moreover, there is no difference in toxicity, therapeutic effects as well as AUC between AMSA--DNA and AMSA.