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通过碱性洗脱和既定检测方法测定阿霉素对P388淋巴细胞白血病的细胞毒性。

Doxorubicin cytotoxicity to P388 lymphocytic leukemia as determined by alkaline elution and established assays.

作者信息

Russo P, Favoni R E, Zarcone D, Miglietta L, Peluso M, Nicolin A, Bignone F, Parodi S

出版信息

Anticancer Res. 1986 Nov-Dec;6(6):1297-304.

PMID:3813486
Abstract

Very large variations exist in the response of individual tumors to antineoplastic agents, even when the tumors are apparently very similar from the point of view of stage and histological classification. It has been recognized for a long time that methods capable of revealing the specific chemosensitivity of individual tumors could be useful for an individual optimization of a chemotherapeutic protocol. The Tumor Colony Forming Assay (TCFA) and the Biochemical Antimetabolic Assay (BAA) have been proposed for this purpose. Their main limitation is a consequence of the fact that the capability of in vitro growth is required from cells of a tumor grown in vivo. This is often lacking or very poor in the first in vitro passages. In this work we have investigated the possibility of using a sensitive method for evaluating DNA damage, the Alkaline Elution technique (AE). Cells treated in vivo can be easily tested directly for DNA damage. No cell proliferation in vitro is required. It is not required that the measured effect is the specific cause of cell death. A P388 Doxorubicin sensitive line and a resistant subline were tested. Correct correlations between DNA damage and chemosensitivity were obtained working both in vivo and in vitro. This test could be useful for assessing the chemosensitivity in vivo of alkylating and intercalating agents.

摘要

即使从分期和组织学分类的角度来看肿瘤明显非常相似,个体肿瘤对抗肿瘤药物的反应仍存在很大差异。长期以来人们已经认识到,能够揭示个体肿瘤特异性化学敏感性的方法对于化疗方案的个体化优化可能是有用的。为此已提出肿瘤集落形成试验(TCFA)和生化抗代谢试验(BAA)。它们的主要局限性是由于在体内生长的肿瘤细胞需要具备体外生长能力这一事实导致的。在最初的体外传代中,这种能力通常缺乏或非常差。在这项工作中,我们研究了使用一种评估DNA损伤的灵敏方法——碱性洗脱技术(AE)的可能性。体内处理过的细胞可以很容易地直接检测DNA损伤。不需要体外细胞增殖。也不要求所测量的效应是细胞死亡的特定原因。对一个P388阿霉素敏感株系和一个耐药亚株系进行了测试。在体内和体外实验中,均获得了DNA损伤与化学敏感性之间的正确相关性。该试验对于评估烷化剂和嵌入剂在体内的化学敏感性可能是有用的。

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Doxorubicin cytotoxicity to P388 lymphocytic leukemia as determined by alkaline elution and established assays.通过碱性洗脱和既定检测方法测定阿霉素对P388淋巴细胞白血病的细胞毒性。
Anticancer Res. 1986 Nov-Dec;6(6):1297-304.
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Clin Pharmacokinet. 1988 Jul;15(1):15-31. doi: 10.2165/00003088-198815010-00002.
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