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一种使培养的哺乳动物细胞的质膜通透化的新方法。IV. 在涡旋搅拌条件下,高分子量聚合物增强博来霉素对哺乳动物细胞细胞毒性的结构要求。

A new method for permeabilization of the plasma membrane of cultured mammalian cells. IV. Structural requirement for high molecular weight polymers for potentiation of bleomycin cytotoxicity toward mammalian cells under conditions of vortex-stirring.

作者信息

Shimizu N, Nakamura M, Azuchi M, Okada M, Kawazoe Y

机构信息

Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.

出版信息

Biol Pharm Bull. 1996 Sep;19(9):1126-9. doi: 10.1248/bpb.19.1126.

Abstract

As we previously reported, the cytotoxicity of bleomycin (BLM) toward cultured mammalian cells was extraordinarily potentiated when the cells and BLM were vortex-stirred for a few seconds in the presence of high molecular weight polyacrylic acid (PAA). Cationic and nonionic polymers could not take the place of PAA in potentiating BLM cytotoxicity. The present study revealed that potentiation was sharply dependent on the molecular weight of PAA and a molecular weight of over 10(6) daltons seemed to be required. Copolymers of acrylic acid (AA) and acrylamide showed some potentiation which was relative to their AA content. It is worth noting that another type of anionic polymer, polymethacrylic acid, did not show any potentiating capacity at all. Polyacrylic sulfonate derivative showed a marginal capacity. The structural requirement for high molecular weight polymers for potentiation of BLM cytotoxicity was demonstrated by the increased uptake of Lucifer Yellow, a non-permeant material. In addition, the ability of permeabilization was not correlated with kinematic viscosity of anionic polymers.

摘要

正如我们之前所报道的,当在高分子量聚丙烯酸(PAA)存在的情况下,将细胞与博来霉素(BLM)涡旋搅拌几秒钟时,博来霉素(BLM)对培养的哺乳动物细胞的细胞毒性会显著增强。阳离子和非离子聚合物在增强BLM细胞毒性方面无法替代PAA。本研究表明,增强作用强烈依赖于PAA的分子量,似乎需要超过10⁶道尔顿的分子量。丙烯酸(AA)和丙烯酰胺的共聚物表现出一定的增强作用,这与它们的AA含量有关。值得注意的是,另一种阴离子聚合物聚甲基丙烯酸根本没有表现出任何增强能力。聚丙烯磺酸盐衍生物表现出微弱的能力。通过一种非渗透性物质路西法黄摄取量的增加,证明了高分子量聚合物增强BLM细胞毒性的结构要求。此外,通透能力与阴离子聚合物的运动粘度无关。

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