Influence of some DNA-alkylating drugs on thermal stability, acid and osmotic resistance of the membrane of whole human erythrocytes and their ghosts.
Human erythrocytes and their resealed ghosts were alkylated under identical conditions using three groups of alkylating antitumor agents: mustards, triazenes and chloroethyl nitrosoureas. Osmotic fragility, acid resistance and thermal stability of membranes were changed only in alkylated ghosts in proportion to the concentration of the alkylating agent. All the alkylating agents decreased acid resistance in ghosts. The clinically used drugs sarcolysine, dacarbazine and lomustine all decreased osmotic fragility and thermal stability of ghost membranes depending on their lipophilicity. DM-COOH did not decrease osmotic fragility and thermal stability of ghost membranes, while NEM increased thermal stability of membranes. The preliminary but not subsequent treatment of ghosts with DM-COOH fully abolished the alkylation-induced thermal labilization of ghost membrane proteins while NEM had a partial effect only. The present study gives direct evidence that alkylating agents, having a high therapeutic activity against malignant growth, bind covalently to proteins of cellular membranes.
Ivanov
I T
IT
Department of Physics and Biophysics, Medical Institute of Thracian University, Stara Zagora, Bulgaria. ivanov_it@hotmail.com
Gadjeva
V
V
D000477:Alkylating Agents / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009150:Mustard Compounds / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000494:pharmacology; D009996:Osmotic Fragility / Q000187:drug effects; D011489:Protein Denaturation / Q000187:drug effects; D014226:Triazenes / Q000494:pharmacology
D000477:Alkylating Agents; D009150:Mustard Compounds; D009607:Nitrosourea Compounds; D014226:Triazenes; D004247:DNA