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.
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.
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
N
N
Shimizu
M
M
Nakamura
M
M
Azuchi
M
M
Okada
Y
Y
Kawazoe
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D002478:Cells, Cultured; D007546:Isoquinolines; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014783:Viscosity
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; D011108:Polymers; D001761:Bleomycin; C017475:lucifer yellow