Effect of potential cytostatic and immune modulating chemicals on the plasma membrane of red blood cells (RBC) as revealed by osmotic hemolysis, cell electrophoresis and scanning electron microscopy (SEM).
The influence on red blood cells (RBC) of two cancerostatic-(ZIMET 3106 and ZIMET 3393) and two immunomodulating agents (ZIMET 3164 and ZIMET 86/76) administered subcutaneously, or intraperitoneally in case of the radiolabelled N-mustard compounds, to mice, was studied by means of measurements of the radiolabelled compounds in blood, by cell electrophoresis, filipin-induced hemolysis of pretreated RBC and by scanning electronmicroscopy. The portion of doses applied which binds to RBC-surface decreases in the sequence of ZIMET 3106, ZIMET 3164, ZIMET 3393 and ZIMET 86/76. However, the highest reduction of the electrophoretic mobility and protection from filipin-induced hemolysis of pretreated RBC was found with ZIMET 3164. In both tests ZIMET 86/76 proved to be ineffective. These findings are in good agreement with the modifications demonstrated in pretreated RBC after filipin-induced hemolysis by means of SEM. The results presented point to a N-mustard specific interaction between the cholesterol of the membrane and/or other membrane constituents. However, these fundamental differences found in binding affinity, surface-charges and membrane interactions caused by the chemically similar compounds cannot be attributed merely to the N-mustard group.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology*; D004586:Electrophoresis; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000648:ultrastructure; D004912:Erythrocytes / Q000187:drug effects*; D005372:Filipin / Q000494:pharmacology; D006461:Hemolysis; D007166:Immunosuppressive Agents / Q000378:metabolism; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009588:Nitrogen Mustard Compounds / Q000378:metabolism / Q000494:pharmacology*; D011806:Quinolinium Compounds / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D007166:Immunosuppressive Agents; D009588:Nitrogen Mustard Compounds; D011806:Quinolinium Compounds; D005372:Filipin