Sava G, Giraldi T, Lassiani L, Nisi C
Cancer Treat Rep. 1982 Sep;66(9):1751-5.
Mice bearing TLX5 lymphoma or P388 leukemia were treated with ortho, meta, and para isomers of the salts of (3,3-dimethyl-1-triazeno)benzoic acid. Survival time was markedly increased in mice given the para isomer; effects were less pronounced for the meta isomer and absent for the ortho isomer. The in vivo effects of the tested compounds did not correlate either with the propensity of the drugs to undergo oxidative N-demethylation and hydrolysis to diazonium cations or with in vitro cytotoxicity for TLX5 lymphoma cells. The para isomer did not reduce the number and viability of peritoneal TLX5 lymphoma cells after in vivo and in vitro treatment, whereas a dose-dependent reduction that can even result in the absence of clonogenic tumor cells occurred in the brains of the treated animals. These data indicate that the increased survival time of the tumor-bearing mice treated with the para isomer should not be ascribed to cytotoxic effects of the drug and might be attributed to inhibition of tumor cell dissemination in various organs of the host, as already observed for solid metastasizing tumors in mice.
携带TLX5淋巴瘤或P388白血病的小鼠用(3,3 - 二甲基 - 1 - 三氮烯)苯甲酸的盐的邻位、间位和对位异构体进行治疗。给予对位异构体的小鼠存活时间显著延长；间位异构体的效果较不明显，邻位异构体则无效果。所测试化合物的体内作用既不与药物进行氧化N - 去甲基化和水解为重氮阳离子的倾向相关，也不与对TLX5淋巴瘤细胞的体外细胞毒性相关。对位异构体在体内和体外处理后并未减少腹膜TLX5淋巴瘤细胞的数量和活力，而在接受治疗的动物大脑中发生了剂量依赖性的减少，甚至可能导致无克隆性肿瘤细胞。这些数据表明，用对位异构体治疗的荷瘤小鼠存活时间延长不应归因于药物的细胞毒性作用，可能归因于抑制肿瘤细胞在宿主各器官中的扩散，这在小鼠实体转移性肿瘤中已观察到。
