Research on the study of membrane toxicity has advanced a great deal in a relatively short period of time, prompting scientists to re-examine the problems associated with carriers, receptors and reactors to toxic substances. This book presents current research on the responses of membranes to toxic sub stances both by direct observation of macromolecules reacting with these substances and by inference from data on the bio chemical responses of cells and cell fractions. Two basic areas of membrane toxicity are analyzed by a large number and variety of scientists in this field. The first area is the effect of various toxic substances on membrane structure and function. The second area is where the membrane serves as the site of rate limiting step of the transport of various toxic substances. The aim of the book is to evaluate present concepts of membrane structure and function in relation to exposure to envir onmental toxicants. The book is divided into five sessions: 1. Xenobiotics and Membrane Transport 2. Cellular Responses to Toxins 3. Effects of Membranes and Receptors 4. Modification of Membrane Function by Toxicological Agents 5. Toxic Chemicals as Molecular Probes of Membrane Structure and Function Each paper is generally concluded by an edited discussion which contains many useful and interesting additional insights in each subject area. v ACKNOWLEDGEMENT We gratefully acknowledge the support provided for this conference by the U. S. Energy Research and Development Administration, the Environmental Protection Agency and the University of Rochester.
Table of Contents
Section I. Xenobiotics and Membrane Transport.- Effect of P-Chloromercuribenzoate (pCMB), Ouabain and 4-Acetamido-4?ISO-Thiocyamatostilbene-2,2?-Disulfonic Acid (Sits) on Proximal Tubular Transport Processes.- Heavy Metals and Membrane Functions of an Alveolar Epithelium.- The Localization of Ion-Selective Pumps and Paths in the Plasma Membranes of Turtle Bladders.- Membrane Water Channels and SH-Groups.- Membrane Transport of Antifolates as a Critical Determinant of Drug Cytotoxicity.- Section II. Modification of Membrane Function by Toxicological Agents.- Liver Endoplasmic Reticulum: Target Site of Halocarbon Metabolites.- The Role of Membrane Damage in Radiation-Induced Cell Death.- Mechanisms by Which Small Molecules Alter Ionic Permeability Through Lipid Bilayer Membranes.- Effects of Neomycin on Polyphosphoinositides in Inner Ear Tissues and Monomolecular Films.- High Affinity SH-Groups on the Surface of Pancreas Cells Involved in Secretin Stimulation.- Section III. Cellular Responses to Toxins.- Cell Membranes in Cytotoxicity.- Altered Drug Permeability in Mammalian Cell Mutants.- Lectin Receptors and Lectin Resistance in Chinese Hamster Ovary Cells.- Biological Applications and Evolutionary Origins of Ionophores.- Penicillin-Binding Proteins of Bacteria.- Section IV. Toxic Chemicals as Molecular Probes of Membrane Structure and Function.- Toxic Chemical Agents as Probes for Permeation Systems of the Red Blood Cell.- Chemical and Enzymatic Modification of Membrane Proteins and Anion Transport in Human Red Blood Cells.- On the Nature of the Transport Pathway Used for Ca-Dependent K Movement in Human Red Blood Cells.- Toxic Chemicals as Probes of Nerve Membrane Function.- Section V. Effects on Membranes and Receptors.- Interactions of Acetylcholine Receptors with Organic Mercury Compounds.- Lead Actions on Sodium-Plus-Potassium-Activated Adenosinetriphosphatase from Electroplax, Rat Brain, and Rat Kidney.- Lipid Model Membrane Studies on Immune Cytotoxic Mechanisms.- Diffusional Transport of Toxic Materials in Membranes Studied by Fluorescence Spectroscopy.- Author Index.