Effect of vinblastine on cell membrane fluidity in vinblastine-sensitive and -resistant HeLa cells.

The electron paramagnetic resonance method (EPR) was used to study the effects of vinblastine (VLB) on cell membrane fluidity in wild-type HeLa cells (HeLa K) and its subclone, which is resistant to several drugs (HeLa CA). HeLa CA cells, obtained by treatment of HeLa K with CDDP, were found to be more resistant to VLB than to CDDP. The experimentally observed EPR spectra were correlated with the calculated spectra obtained by computer simulation. The results indicate that the cell membrane of HeLa K and HeLa CA cells is heterogeneous and can be described with at least three types of coexisting domains with different fluidity characteristics. The two more fluid domains of HeLa CA cells were found to be more fluid than in HeLa K cells. The fluidity of the less fluid domain remained unchanged but its portion in the membrane was increased. VLB treatment did not affect the membrane fluidity of HeLa CA cells significantly. On the other hand, 1 h of treatment of HeLa K cells with 1 ng/ml VLB did not change the fluidity characteristics of membrane domains but decreased the portion of the less fluid domains. This was also reflected in an average increase of the entire membrane fluidity. The observed changes were detected at VLB concentrations which were far below the cytotoxic level.