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新型蒽环类衍生物对正常骨髓髓系祖细胞(CFU-GM)的毒性不会因维拉帕米而增加。

Toxicity of novel anthracycline derivatives towards normal myeloid bone marrow progenitor cells (CFU-GM) is not increased by verapamil.

作者信息

Busch F W, Schmittele U, Ehninger G

机构信息

Medizinische Universitätsklinik, Tübingen, Federal Republic of Germany.

出版信息

Blut. 1990 Apr;60(4):219-22. doi: 10.1007/BF01728787.

DOI:10.1007/BF01728787
PMID:2337680
Abstract

Drug-induced myelotoxicity is usually the dose-limiting factor of treatment of malignant tumors with cytostatic drugs. Suppression of in vitro myelopoiesis (CFU-GM) by cytostatics may be a suitable model reflecting the in vivo situation. Thus the inhibitory effects of the anthracyclines doxorubicin, theprubicin, idarubicin and cytorhodin S on CFU-GM were compared. Normal human bone marrow cells were incubated with these drugs for one hour and alternatively, for the whole culture period. For each substance and each incubation time a dose-response curve was established and the D50 determined. As certain calcium antagonists can increase the toxicity of some cytostatic drugs in various tumor models, the effect of the addition of verapamil (2 microM) was also investigated. It could be shown, that the myelotoxicity on CFU-GM of the drugs mentioned above was not increased after short-term or permanent exposure to this calcium antagonist.

摘要

药物诱导的骨髓毒性通常是细胞毒性药物治疗恶性肿瘤的剂量限制因素。细胞毒性药物对体外骨髓生成(CFU-GM)的抑制作用可能是反映体内情况的合适模型。因此,比较了蒽环类药物阿霉素、丙亚胺、伊达比星和柔红霉素S对CFU-GM的抑制作用。将正常人骨髓细胞与这些药物孵育1小时,或者在整个培养期间孵育。对于每种物质和每个孵育时间,建立剂量反应曲线并确定D50。由于某些钙拮抗剂在各种肿瘤模型中可增加某些细胞毒性药物的毒性,因此还研究了添加维拉帕米(2 microM)的效果。结果表明,在短期或长期暴露于这种钙拮抗剂后,上述药物对CFU-GM的骨髓毒性并未增加。

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本文引用的文献

1
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Plasma pharmacokinetics of adriamycin and adriamycinol: implications for the design of in vitro experiments and treatment protocols.阿霉素和阿霉素醇的血浆药代动力学:对体外实验设计和治疗方案的启示
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Cancer Res. 1983 Dec;43(12 Pt 1):6096-101.
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Reversal of adriamycin resistance by verapamil in human ovarian cancer.维拉帕米逆转人卵巢癌对阿霉素的耐药性。
Science. 1984 Jun 1;224(4652):994-6. doi: 10.1126/science.6372095.
5
Flow cytometric monitoring of cellular anthracycline accumulation in murine leukemic cells.流式细胞术监测小鼠白血病细胞中蒽环类药物的细胞内蓄积情况。
Cancer Res. 1986 Apr;46(4 Pt 1):1768-73.
6
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Cancer Res. 1985 Oct;45(10):4921-4.
7
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8
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