Zimber A, Perk K, Livnat I
Department of Animal Science, Faculty of Agriculture, Israel.
Br J Cancer. 1988 Mar;57(3):266-70. doi: 10.1038/bjc.1988.57.
Pretreatment of mice with low doses of methyl-CCNU was shown to reduce the toxicity of lethal doses of methyl-CCNU or melphalan administered one or two days following the low dose. There was an increase in survival rate, body weight, thymus and kidney wet weight. Tissue morphology was less affected in the primed mice as compared to mice receiving the high dose or a high-low dose combination. In mice implanted s.c. with Lewis lung carcinoma, priming with 5 mg kg-1 methyl-CCNU 2 days before injection of a very high (35 mg kg-1) dose significantly increased the lifespan as compared to treatment with the high dose alone or with high-low dose combination. When the dose of methyl-CCNU was further increased to 40 mg kg-1 toxic death occurred, which was, however, significantly reduced by 'priming' with the low dose given. When low-high dose combination was used twice (the high dose was given on day 7 or 9, and 18 or 20 after tumour inoculation), priming with 5 mg kg-1 (but not with 10 mg kg-1) two days prior to the high dose was beneficial in reducing toxic death (in two experiments) and either increasing lifespan or not significantly increasing it. In no case was there protection of the tumour by the low-high dose combinations.
低剂量甲基环己亚硝脲预处理小鼠，可降低在低剂量后1天或2天给予致死剂量的甲基环己亚硝脲或美法仑的毒性。存活率、体重、胸腺和肾脏湿重均有所增加。与接受高剂量或高低剂量组合的小鼠相比，预处理小鼠的组织形态受影响较小。在皮下植入Lewis肺癌的小鼠中，与单独使用高剂量或高低剂量组合治疗相比，在注射非常高剂量（35 mg kg-1）前2天用5 mg kg-1甲基环己亚硝脲预处理可显著延长生存期。当甲基环己亚硝脲剂量进一步增加到40 mg kg-1时会发生毒性死亡，然而，通过低剂量“预处理”可显著降低毒性死亡。当高低剂量组合使用两次时（高剂量在接种肿瘤后第7天或第9天以及第18天或第20天给予），在高剂量前2天用5 mg kg-1（而不是10 mg kg-1）预处理有利于降低毒性死亡（在两个实验中），并且要么延长生存期，要么没有显著延长生存期。高低剂量组合在任何情况下都不会对肿瘤起到保护作用。
