Molecular Pharmacology, Vol 14, 1121-1129, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Effect of Dithiocarbanilates on Some Biological and Biophysical Properties of Leukemia L1210 Cell Membranes

¹ Departments of Oncology and Pharmacology, Wayne State University School of Medicine, and Michigan Cancer Foundation, Detroit, Michigan 48201, and Medical Research Council of Ireland, Trinity College, Dublin 2, Ireland

This study was designed to seek correlations between membrane alterations detected by transport studies and those measured by two biophysical techniques. A group of substituted dithiocarbanilates was found to alter selectively different membrane properties related to permeability and transport. We found a correlation between disruption of a membrane permeability barrier to accumulation of actinomycin D and an enhanced fluorogenic interaction between cells and a dansyl cadaverine probe. Inhibition of facilitated diffusion of nucleosides across the cell membrane was correlated with a more "hydrophobic" cell surface, detected by two-phase aqueous polymer partitioning studies in an "uncharged" system. Inhibition of active transport of a model amino acid, cycloleucine, was correlated with reduced cell-surface and membrane charge, detected by two-phase partitioning studies in a "charged" system. Dithiocarbanilates that caused inhibition of amino acid transport also quenched the fluorogenic cell interaction with dansyl cadaverine, suggesting a more generalized chaotropic drug effect. These findings suggest loci of membrane processes regulating permeability, and of barriers to substrate movement within the cell membrane.