Toxicity of cytostatic drugs to normal bone marrow cells in vitro

Toxicity of cytostatic drugs to normal bone marrow cells in vitro
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细胞抑制剂对正常骨髓细胞的体外毒性

DOI:
10.1007/s002800050779
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发表时间:
1998
影响因子:
3
通讯作者:
C. Paul
C. Paul
中科院分区:
医学3区
文献类型:
--
作者:
B. Sundman;U. Tidefelt;C. Paul

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摘要在这项研究中,我们比较了蒽环类抗生素、安吖啶和阿糖胞苷的不同浓度和孵育时间对正常造血骨髓细胞的毒性、供体年龄和骨髓增殖能力的个体间差异。从与骨髓移植相关的36个供体获得骨髓。分离后,将单核细胞级分与多柔比星、4-表多柔比星、柔红霉素、伊达比星、阿克拉霉素、米托蒽醌、安吖啶和阿糖胞苷孵育1小时、3小时或连续孵育。然后在软琼脂中培养细胞,10 - 12天后计数CFU-GM。结果表明,所有测试药物的毒性存在较大的个体间差异。柔红霉素、伊达比星、阿克拉霉素和米托蒽醌在孵育1小时后具有明显的细胞毒性作用。阿霉素和4-表阿霉素在3小时后显示出最大的细胞毒性作用,并且对40岁以上供体的正常骨髓细胞也更具毒性。Ara-C在孵育1小时和3小时后具有低细胞毒性效应,即使在高浓度下也是如此,但在连续孵育过程中具有明显的毒性。柔红霉素、伊达比星和阿糖胞苷也显示出对对照组中增殖能力低的细胞样品的毒性增加。从这些结果中得出的结论是,个体间的差异,增殖能力,孵育条件,和年龄的捐助者的药物对正常造血骨髓细胞的毒性的重要因素。
Abstract In this study we compared how different concentrations and periods of incubation of anthracyclines, amsacrine, and cytosine arabinoside would affect normal hematopoietic bone marrow cells in terms of interindividual differences in toxicity, the age of the donor, and the proliferative capacity of the bone marrow. Bone marrow was obtained from 36 donors in connection with bone marrow transplantation. After separation the mononuclear cell fraction was incubated with doxorubicin, 4-epidoxorubicin, daunorubicin, idarubicin, aclarubicin, mitroxantrone, amsacrine, and cytosine arabinoside for 1 h, for 3 h, or continuously. The cells were thereafter cultured in soft agar and CFU-GM were counted after 10–12 days. The results showed a large interindividual variation in toxicity for all drugs tested. Daunorubicin, idarubicin, aclarubicin, and mitoxantrone had a pronounced cytotoxic effect after 1 h of incubation. Doxorubicin and 4-epi-doxorubicin showed the greatest cytotoxic effect after 3 h and were also more toxic to normal bone marrow cells from donors over 40 years of age. Ara-C had a low cytotoxic effect after 1 and 3 h of incubation, even at high concentrations, but exerted a pronounced degree of toxicity during continuous incubation. Daunorubicin, idarubicin, and ara-C also showed increased toxicity to cell samples with a low proliferating capacity in the control. The conclusions drawn from these results are that interindividual variation, proliferation capacity, incubation conditions, and the age of the donors are factors of importance in the toxicity of drugs to normal hematopoietic bone marrow cells.
DOI: --
发表时间: 1986-03
期刊: Cancer research
影响因子: 11.2
作者:
J. Liliemark;W. Plunkett
通讯作者: J. Liliemark;W. Plunkett
DOI: 10.1126/science.6093249
发表时间: 1984-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
TEWEY, KM;ROWE, TC;LIU, LF
通讯作者: LIU, LF
实验化疗和与细胞周期相关的概念。
DOI: 10.1080/09553008514552581
发表时间: 1986
期刊: International journal of radiation biology and related studies in physics, chemistry, and medicine
影响因子: --
作者:
Tannock,IF
通讯作者: Tannock,IF