A new method for permeabilization of the plasma membrane of cultured mammalian cells. VI. Enhanced cytotoxicity of bleomycin toward leukemia P388 cells inoculated into the tail vein of mice together with high molecular weight polyacrylic acid--similarity of blood stream to vortex-stirring.

Abstract

Bleomycin (BLM) cytotoxicity was greatly enhanced by vortex-stirring BLM and mammalian cells for a few seconds together with 1 to 10 microg/ml high molecular weight polyacrylic acid (A-119). When suspensions of murine leukemia P388 cells were injected together with BLM and A-119 into the tail vein of CDF1 mice, cell viability was reduced to 1/1000, the reduction being similar to that obtained by vortex-stirring the cells with BLM and A-119 in vitro. This was corroborated by an increase in the survival time of these mice. The reduction in cell viability was noted only when the cells, BLM, and A-119 were simultaneously injected. There was absolutely no effect when there was a time-lag between cell inoculation and injection of BLM/A-119. These findings suggest that the conditions created by the blood stream may simulate those of vortex-stirring and that, in both cases, rapid uni-directional movement of cells with high molecular weight polyacrylic acid may affect the plasma membrane facilitating internalization of non-permeant materials into cells.