Induction of Activated Macrophages by Intraperitoneal Injection of MMC-CH, Mitomycin C Adsorbed on Activated Carbon Particles

本研究考察了吸附在活性炭颗粒上的丝裂霉素C （MMC- ch）腹腔注射对宿主免疫状态和腹腔巨噬细胞（PM）细胞溶解活性的影响，并将其与MMC溶液（MMC- aq）本身进行了比较。MMC-CH组小鼠脾脏和胸腺重量的下降幅度小于MMC-AQ组。MMC-AQ组小鼠脾细胞对Con A的反应性比MMC-CH组小鼠大。给予MMC-AQ小鼠50%致死剂量为8 mg/kg，给予MMC-CH小鼠50%致死剂量为16 mg/kg。单次IP注射MMC-AQ或MMC-CH诱导腹腔内的肿瘤杀伤巨噬细胞。其抑瘤活性与注射MMC的剂量和效应靶比有关，并受卡拉胶的抑制。MMC-AQ组和MMC-CH组在时间上的pec变化有显著差异。注射MMC-AQ IP后1 d， PEC数量明显减少，而注射MMC-CH后PEC数量增加，是注射MMC-AQ后的10倍。还观察到PM的细胞溶解活性的时间变化有显著差异。在注射MMC-CH的情况下，PM的细胞溶解活性比MMC-AQ保持的时间更长。在MMC- aq和MMC- ch注射小鼠的超声PM可溶部分中检测到MMC，这些可溶部分对靶细胞有杀瘤作用。基于这些结果，我们认为mmc诱导的PM中有一定的细胞内药物参与了肿瘤作用，特别是注射MMC-CH后。

In this study, we examined the effect on the immunological status of hosts and on the cytolytic activity induced in the peritoneal macrophage(PM) by intraperitoneal(IP) injection of MMC-CH, Mitomycin C adsorbed on activated carbon particles and compared it with that of the MMC solution(MMC-AQ) itself. The weight of spleen and thymus of the mice given MMC-CH was decreased lesser than those of the mice given MMC-AQ. Reactivity of spleen cells by Con A was inhibited in the spleen cells from the mice given MMC-AQ more than that from the mice given MMC-CH. Fifty per cent lethal dose was 8 mg/kg in the mice given MMC-AQ, and 16 mg/kg in the mice given MMC-CH. Single IP injection of either MMC-AQ or MMC-CH induced tumoricidal macrophage in the peritoneal cavity. The tumoricidal activity was dependent on the dose of MMC injected and on the effector-to-target ratio and was suppressed by the presence of carrageenan. A significant difference was found in the chronological change of pec between MMC-AQ and MMC-CH administration. One day after MMC-AQ IP injection, the number of PEC wasdecreased markedly, however, it was increased after MMC-CH injection and the number was ten times more than that of MMC-AQ injection. A marked difference in the chronological change of the cytolytic activity of the PM was also observed. In the case of MMC-CH injection, cytolytic activity of PM remained high longer time than that of MMC-AQ. MMC was detected in the soluble fraction of ultrasonicated PM from either MMC-AQ or MMC-CH injected mice and these soluble fraction had a tumoricidal effect on the target cells. Based on these results, it was concluded that there is some participation of intra-cellular drug within the MMC-induced PM in tumoriciadal effects, especially after MMC-CH injection.