Marsh J C, Brown B J, Nierenburg M M
Cancer Res. 1983 Jun;43(6):2962-6.
The sensitivity of bone marrow granulocyte-macrophage colony-forming cells to 4 anthracyclines, carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin, was studied using the agar diffusion chamber technique which allows exposure of target cells to drug metabolized by the chamber-bearing host after i.v. injection. Colony-forming cells from mice, dogs, and humans were all found to have exponential dose-response curves for the agents studied, with variation of the slopes between species and agents. Species sensitivities as determined by the assay related well to the available toxicological and clinical data for specific drugs. The rank order of sensitivity of human marrow colony-forming cells to five anthracyclines tested in this and a previous study related very closely to doses producing moderate leukopenia in Phase I and II clinical studies. A dose of 200 mg/sq m of N,N-dibenzyldaunorubicin would be expected to produce moderate leukopenia in future clinical trials. This assay may be useful in predicting human bone marrow toxicity of new agents before actual clinical trial because of the ability to study the survival of human colony-forming cells directly.
采用琼脂扩散室技术研究了骨髓粒-巨噬细胞集落形成细胞对4种蒽环类药物（卡米诺霉素、马塞洛霉素、阿克拉霉素A和N，N-二苄基柔红霉素）的敏感性，该技术可使靶细胞在静脉注射后接触由携带扩散室的宿主代谢的药物。小鼠、犬和人的集落形成细胞对所研究的药物均呈现指数剂量反应曲线，不同物种和药物之间斜率有所差异。通过该测定法确定的物种敏感性与特定药物现有的毒理学和临床数据密切相关。在本研究及之前的一项研究中，人类骨髓集落形成细胞对5种蒽环类药物的敏感性排序与I期和II期临床研究中导致中度白细胞减少的剂量密切相关。在未来的临床试验中，预计200mg/m²的N，N-二苄基柔红霉素剂量会导致中度白细胞减少。由于能够直接研究人类集落形成细胞的存活情况，该测定法可能有助于在实际临床试验之前预测新药对人类骨髓的毒性。
