Adsorption to human red blood cells of chlorambucil and other biological alkylating agents

Abstract

Utilizing the red blood cell as a model system, a study was made of the uptake of several alkylating agents and of certain biologically inert derivatives of these agents. The results suggest that the chloroethyl group binds to the surface of the cell presumably by virtue of its fat solubility. Adsorption or uptake by the cell takes place independently of alkylation, which may follow at a slower rate. The binding associated with the presence of the chloroethyl group is of a specific type which involves a surface solubility action. This has a potentially disruptive effect on the cell surface which is not associated with the binding of the substance by the Van der Waals type of adsorptive forces. When the molecule that is bound to the cell surface by the action of the chloroethyl group also carries a negative charge, the cell membrane may undergo complete disruption. From the pharmacological point of view, the binding of drugs to the cell may be of importance because the process serves to remove the drug temporarily from the action of nucleophilic substances in the body fluids. Of the compounds tested, only those with a net negative charge were able to bring about hemolysis after adsorption to the red cell.