Marsh J C
Exp Hematol. 1985;13 Suppl 16:16-22.
The effects of 22 anticancer agents on bone marrow granulocyte-macrophage-committed colony-forming cells (CFC) have been studied using the agar diffusion chamber (ADC) assay, which allows in vivo metabolism of the injected drug by the chamber-bearing mouse. Dose-response curves at 18 h were obtained using mouse, dog, and human bone marrow in the chamber, and mouse marrow in situ. Comparisons between intrinsic sensitivities of CFC from different species were thus possible, as were also comparisons of the effect of different drugs on the same species. When possible, correlations were made with available in vivo clinical or toxicologic data, using the effect of a single intravenous dose on the blood granulocyte concentration. Dose-response curves were either exponential or formed a plateau, the latter reflecting phase specificity of the agent being studied. Species CFC sensitivities were highly variable between different drugs and the order was not predictable. Good correlation between rank order of drug efficacy in vivo and in the assay was observed for drugs in the same species. Drugs with little or no myelosuppressive effects in vivo were likewise inactive in the assay (e.g., spirogermanium). Prospective trials of new agents in the drug development process (toxicology and phase-I clinical trials) using the ADC assay are warranted.
利用琼脂扩散盒（ADC）试验研究了22种抗癌药物对骨髓粒细胞-巨噬细胞定向集落形成细胞（CFC）的影响，该试验可使携带扩散盒的小鼠对注入的药物进行体内代谢。使用盒内的小鼠、犬和人骨髓以及原位小鼠骨髓，获得了18小时时的剂量反应曲线。因此，既可以比较不同物种CFC的内在敏感性，也可以比较不同药物对同一物种的影响。在可能的情况下，利用单次静脉给药对血液粒细胞浓度的影响，将其与现有的体内临床或毒理学数据进行相关性分析。剂量反应曲线要么呈指数形式，要么形成平台期，后者反映了所研究药物的阶段特异性。不同药物之间，物种CFC的敏感性差异很大，且顺序无法预测。在同一物种中，观察到体内药物疗效的排序与试验中的排序具有良好的相关性。在体内几乎没有或没有骨髓抑制作用的药物在试验中同样无活性（例如，螺锗）。有必要在药物研发过程（毒理学和I期临床试验）中使用ADC试验对新药物进行前瞻性试验。
