Sava G, Giraldi T, Lassiani L, Nisi C, Farmer P B
Biochem Pharmacol. 1982 Nov 15;31(22):3629-34. doi: 10.1016/0006-2952(82)90586-x.
DM-CONH2, a dimethyltriazene active in prolonging the survival time of mice bearing TLX5 lymphoma, requires metabolic activation by liver homogenate supernatant and cofactors in order to exert in vitro cytotoxic effects on the same tumor cells, as determined by in vivo bioassay of their viability. From the examination of the metabolites produced during these in vitro experiments, it is found that in vitro cytotoxicity is attributable to the generation of MM-CONH2 by oxidative N-demethylation of DM-CONH2. Also the generation of DM-COO is observed, although this compound is not cytotoxic in vitro. The in vivo effects of DM-CONH2 and CM-COOK on TLX5 lymphoma are not caused exclusively by cytotoxic effects of the drugs, since they are evident also when no reduction in the number or viability of peritoneal tumor cells is evident, whereas these parameters are significantly reduced by MM-CONH2. The increase in survival time of mice bearing TLX5 lymphoma caused by the dimethyltriazenes used appears to be caused by the drugs without being subjected to metabolic activation, with a mechanism different from cytotoxicity for tumor cells.
DM - CONH2是一种对携带TLX5淋巴瘤的小鼠具有延长存活时间活性的二甲基三氮烯，根据其体内活力生物测定法，它需要肝脏匀浆上清液和辅因子进行代谢激活，才能对相同的肿瘤细胞发挥体外细胞毒性作用。通过对这些体外实验过程中产生的代谢物进行检测发现，体外细胞毒性归因于DM - CONH2经氧化N - 去甲基化生成MM - CONH2。还观察到了DM - COO的生成，尽管该化合物在体外没有细胞毒性。DM - CONH2和CM - COOK对TLX5淋巴瘤的体内作用并非完全由药物的细胞毒性作用引起，因为当腹膜肿瘤细胞数量或活力没有明显减少时，这些作用也很明显，而MM - CONH2会显著降低这些参数。所用二甲基三氮烯导致携带TLX5淋巴瘤的小鼠存活时间延长，这似乎是由未经代谢激活的药物引起的，其机制不同于对肿瘤细胞的细胞毒性。
