Supino R
Tumori. 1984 Apr 30;70(2):121-6. doi: 10.1177/030089168407000202.
It has been shown that ICRF-159 [1,2-bis(3,5-dioxopiperazine-1-yl)propane] and its more water soluble d-enantiomer, ICRF-186, antagonize the toxicity of daunorubicin and the cardiac toxicity of daunorubicin and doxorubicin and potentiate the antitumor effect of both substances in experimental animals. In particular, the antagonism against general toxicity was observed in combination with daunorubicin but not with doxorubicin. In this study, we evaluated the activity of ICRF-159 and ICRF-186 on the colony inhibition test of HeLa cells in vitro in combination with daunorubicin or doxorubicin. ICRF-159 and ICRF-186 similarly antagonize the cytotoxicity of daunorubicin but not of doxorubicin. There were no differences between ICRF-159 and ICRF-186, dissolved in DMSO and in physiological solution, respectively. The different activity of ICRF-159 and ICRF-186 against daunorubicin and doxorubicin is not explained by a different uptake of the anthracyclines by HeLa cells in vitro. In the present paper we report findings from our in vitro colony forming assay with HeLa cells, which has been used to evaluate the cytotoxicity of ICRF-159 and ICRF-186 in the presence of daunorubicin and doxorubicin.
已表明ICRF - 159 [1,2 - 双(3,5 - 二氧代哌嗪 - 1 - 基)丙烷]及其水溶性更强的d - 对映体ICRF - 186可拮抗柔红霉素的毒性以及柔红霉素和阿霉素的心脏毒性，并增强这两种物质在实验动物中的抗肿瘤作用。特别是，与柔红霉素联合使用时观察到对一般毒性的拮抗作用，但与阿霉素联合使用时未观察到。在本研究中，我们评估了ICRF - 159和ICRF - 186与柔红霉素或阿霉素联合对体外HeLa细胞集落抑制试验的活性。ICRF - 159和ICRF - 186同样拮抗柔红霉素的细胞毒性，但不拮抗阿霉素的细胞毒性。分别溶解于二甲基亚砜和生理溶液中的ICRF - 159和ICRF - 186之间没有差异。ICRF - 159和ICRF - 186对柔红霉素和阿霉素的不同活性不能用HeLa细胞体外对蒽环类药物的不同摄取来解释。在本文中，我们报告了用HeLa细胞进行的体外集落形成试验的结果，该试验已用于评估在柔红霉素和阿霉素存在下ICRF - 159和ICRF - 186的细胞毒性。
