Marsh J C
Cancer Res. 1976 Jun;36(6):1853-82.
The effects of antineoplastic agents, singly or in combination, on normal hematopoietic precursor cells have been reviewed. Following a description of the assays used (e.g., spleen colony, in vitro colony, repopulating ability), the dose response and/or time response for each drug are presented by species and by assay as available. The schedule of drug administration, the time of the assay, and the proliferative state of the target population are the most important determinants. Alkylating agents, antitumor antibiotics, and 5-fluorouracil have exponential dose survival curves. "Phase-specific" agents such as antimetabolites, Vinca alkaloids, and ribonucleotide reductase inhibitors have plateaus in their dose survival curves, although the level of this plateau is different for different agents. Most drugs are more effective against rapidly proliferating cells although busulfan is less effective. Direct interspecies comparisons are possible with some of the clonogenic assays, which may allow prediction of the magnitude of human hematological toxicity for new agents or combinations.
已综述了抗肿瘤药物单独或联合使用对正常造血前体细胞的作用。在描述所使用的检测方法(如脾集落、体外集落、再增殖能力)之后,按物种和现有检测方法列出了每种药物的剂量反应和/或时间反应。给药方案、检测时间和靶细胞群体的增殖状态是最重要的决定因素。烷化剂、抗肿瘤抗生素和5-氟尿嘧啶具有指数剂量存活曲线。“时相特异性”药物如抗代谢物、长春花生物碱和核糖核苷酸还原酶抑制剂在其剂量存活曲线中有平台期,尽管不同药物的该平台期水平不同。大多数药物对快速增殖细胞更有效,尽管白消安的效果较差。一些克隆形成检测可进行直接种间比较,这可能有助于预测新药物或联合用药对人类血液学毒性的程度。