Cooperative sequestration of m-AMSA in L1210 cells.
Cooperative sequestration of m-AMSA in L1210 cells.
复制标题
L1210 细胞中 m-AMSA 的协同隔离。
DOI：
10.1016/0006-2952(82)90561-5
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发表时间：
1982
影响因子：
5.8
通讯作者：
K. Kohn
中科院分区：
文献类型：
--
作者：
L. Zwelling;D. Kerrigan;S. Michaels;K. Kohn
已知抗癌药物4′-(9-acridinylamino)-methanesulfon-m-anisidide(m-amsa)通过插层与dna结合，并在细胞中产生与蛋白质相关的dna链断裂。以前的工作[Zwell ingetal.，BioChemical y20,6553(1981)]已经表明m-AMSA在细胞外和细胞内的隔间快速平衡，DNA链断裂存在于快速形成和重新密封的稳定状态。目前的工作报告了一个不寻常的摄取m-AMSA的小鼠白血病L1210细胞现象，发生在比以前研究的更高的药物浓度。新的摄取现象具有协同性、滞后性、不可逆性、饱和性、迟滞性和温度依赖性。结果表明，m-AMSA浓度高于临界值可引发m-AMSA不可逆的滞留进入一个新的相，可能是在细胞的核外室，药物不能从那里获得核DNA，可能不会对细胞产生毒性。
The anticancer drug 4′-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) is known to bind to DNA by intercalation and to produce protein-associated DNA strand breaks in cells. Previous work [Zwellinget al., Biochemistry20, 6553 (1981)] had shown that m-AMSA is in rapid equilibrium between extracellular and intracellular compartments, and that the DNA strand breaks exist in a steady state of rapid formation and resealing. The current work reports an unusual uptake phenomenon of m-AMSA by mouse leukemia L1210 cells that occurs at higher drug concentrations than previously studied. The new uptake phenomenon was characterized by cooperativity, hysteresis, irreversibility, saturability, slowness and temperature dependence. It is concluded that m-AMSA concentrations above a critical value can initiate the irreversible sequestration of m-AMSA into a new phase, probably in an extranuclear compartment of the cell, from which the drug has no access to the nuclear DNA and probably does not contribute to cytotoxicity.