EFFECT OF VINBLASTINE ON CELL-MEMBRANE FLUIDITY IN VINBLASTINE-SENSITIVE AND VINBLASTINE-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 H eLa cells (HeLa Ii) and its subclone, which is resistant to several dr ugs (HeLa CA). HeLa CA cells, obtained by treatment of HeLa Ii with CD DP, were found to be more resistant to VLB than to CDDP. The experimen tally observed EPR spectra were correlated with the calculated spectra obtained by computer simulation. The results indicate that the cell m embrane of HeLa K and HeLa CA cells is heterogeneous and can be descri bed with at least three types of coexisting domains with different flu idity characteristics. The two more fluid domains of HeLa CA cells wer e found to be more fluid than in HeLa K cells. The fluidity of the les s 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 whi ch were far below the cytotoxic level. (C) 1998 Elsevier Science Irela nd Ltd. All rights reserved.