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Tamoxifen, Anticancer Drug, Erythrocyte Membrane, Phospholipid Bilayer Tamoxifen is a non steroidal antiestrogen drug extensively used in the prevention and treatment of hormone-dependent breast cancer. To evaluate its perturbing effect upon cell membranes it was made to interact with human erythrocytes and molecular models. These consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and of dimyristoylphospha-tidylethanolamine (DMPE), representative of phospholipids classes located in the outer and inner leaflets of the erythrocyte membrane, respectively. Experiments by fluorescence spectroscopy showed that tamoxifen interacted with DMPC vesicles fluidizing both its polar head and acyl chain regions. These results were confirmed by X-ray diffraction which indi­ cated that tamoxifen perturbed the same regions of the lipid. However, it did not cause any significant structural perturbation to DMPE bilayers. The examination by electron micro­ scopy of human erythrocytes incubated with tamoxifen revealed that they changed their normal discoid shape to stomatocytes. According to the bilayer couple hypothesis, this result means that the drug is inserted in the inner leaflet of the erythrocyte membrane. Given the fact that tamoxifen did not interact with DMPE, it is concluded that it interacted with a protein located in the cytoplasmic moiety of the erythrocyte membrane.

The possible interaction of DDT with the lipids dimyristoyl lecithin (DML), dipalmitoylphos-phatidylethanolamine (DPPE) and tripalmitin (TP) was studied. The work was carried out on oriented films and crystalline powders of DDT-lipid mixtures at different molar ratios by X-ray diffraction techniques. The diagrams showed only the patterns of pure DDT and that of the corresponding lipid. It is concluded that new phases were not formed and, therefore, no interactions occurred.

Pentachlorophenol (PCP) is a widely used and highly toxic fungicide. Its toxicity is mainly expressed at the cell membrane level. It is, therefore, of interest to test its ability to alter the lipid bilayer organization. The present study was performed by X-ray diffraction techniques on dimyristoylphosphatidylethanolamine (DMPE) and dimyristoylphosphatidylcholine (DMPC) bilayers and by fluorescence on DMPC liposomes. These two phospholipids are respectively found at the inner and outer monolayers of human erythrocyte membranes. Each type of phospholipid was made to interact with different concentrations of the sodium form of PCP in absence and in presence of water. It was found that PCP significatively affected the structure of both phospholipids, being the damage much higher in DM PC bilayers.

Dieldrin is an organochlorine insecticide highly toxic for human beings. Although its exact mechanism of action is not well known, there is evidence that it acts at the cell membrane level. In fact, the lipophilicity of the pesticide as well as that of the phospholipid bilayer present in biological membranes makes the latter a most likely target for the interaction of dieldrin with living organisms. In order to evaluate its perturbing effect upon cell membranes the pesticide was made to interact with human erythrocytes and molecular models. These studies were performed by scanning electron microscopy on erythrocytes, fluorescence spectroscopy on dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles and X-ray diffraction on multilayers of dimirystoylphosphatidylcholine (DMPC) and dimyristoyl-phosphatidylethanolamine (DMPE). It was observed that dieldrin particularly interacted with DMPC liposomes and multilayers perturbing its molecular arrangements. However, no effect was noticed on erythrocytes, which might be due to its high cholesterol content.

Penicillin G (PEN) is a widely used antibiotic whose mechanism of action is related to the interference with the synthesis of bacteria cell wall. In order to evaluate its perturbing effect upon human cell membranes PEN was made to interact with human erythrocytes, isolated resealed human erythrocyte membranes and molecular models. The latter were multibilayers of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidyl-ethanolamine (DMPE) as well as DMPC large unilamellar vesicles. These studies were per­ formed by scanning electron microscopy, fluorescence spectroscopy and X-ray diffraction methods. The observed results coincide in that PEN did not exert any significant effect upon the structures of the red cell membrane neither on its molecular models. This is in agreement with its reported lack of major toxicity and hem atological reactions.

Chloramphenicol is a widely used antibiotic with low levels of toxicity. However, scanning electron microscopy revealed morphological changes in human erythrocytes when they interacted in vitro with therapeutical concentrations of chloram phenicol. To explain this shape change, a study concerned with the possible interactions of this antibiotic with bilayers built-up of phospholipids located in either side of the red cell membrane was performed by X-ray diffraction. Results indicated that chloramphenicol was unable to perturb in any significant extent the structure of the phospholipids under study. The only noticeable effects were phase transitions produced to dim yristoylphosphatidylethanolamine bilayers.

Oriented films and powder samples of the phospholipid ʟ-α-dipalmitoyl phosphatidylethanol­ amine (DPPE) were studied by X-ray fiber diffraction techniques. The specimens were photographed under a complete range of hydration at room temperature. Two polymorphic forms were found. One of them was present in oriented films. It showed a close packing of DPPE molecules lying parallel to the normal to the bilayer plane. The other form, observed in the powder samples, had the molecules tilted by about 25°. Both forms were characterized by their unit cell dimensions, space groups, molecular conformations and packing arrangements.

Chlorpromazine is a widely used phenothiazine tranquilizer known to alter the shape of normal erythrocytes and their osmotic fragility. In order to understand the nature of the interactions chlorpromazine · HCl (CPZ · HCl) was made to interact with phospholipid bilayers formed by dimyristoylphosphatidylethanolamine (DMPE) and dimyristoylphosphatidylcholine (DMPC). This study was carried out by X-ray diffraction on crystalline powders of various molar mixtures of CPZ · HCl with DMPE and DMPC, with and without water. It was found that CPZ · HCl significatively affects the bilayer structure of DMPC in the presence of water, but not that of DMPE.

Phospholipid, Bilayer, X-Ray Diffraction, Morphology, Dilaurylphosphatidylethanolam ine, Membrane Powder samples and oriented films of the synthetic phospholipid L-α-dilaurylphosphatidyl-ethanolamine (DLPE) were studied by X-ray diffraction over a wide range of hydration. Only small differences were found between the unit cell dimensions of DLPE powder and oriented-film specimens. These dimensions did not vary appreciably with hydration. In the multilayer DLPE structure, the molecules pack with polar groups parallel to the bilayer plane and hydro­ carbon chains perpendicular to it. Examination of oriented films by scanning electron microscopy gave information on the surface morphology. Complementary data on the lamellar packing of the molecules and the average thickness of the bilayers was provided by thin-section and shadow-cast preparations studied by transmission electron microscopy.

This study deals with the structural perturbations that the antibiotic chlortetracycline hy­drochloride (CTC) can produce on phospholipid bilayers. Two multibilayer systems, one built-up of dimyristoylphosphatidylethanolamine (DMPE) and the other of dimyristoylphos-phatidylcholine (DMPC) were allowed to interact with different concentrations of CTC in the absence and presence of water. The study was carried out by X-ray diffraction methods and all experiments were done below the phospholipid main transition temperatures. The results showed that CTC produced significant perturbations on DMPC even in the absence of water, whereas they were much milder in DMPE .

Pentachlorophenol (PCP) is a widely used pesticide, particularly for the preservation of wood. Given its high toxicity and resistance to degradation it has become a dangerous environmental pollulant. Due to its high lipophilicity, PCP is able to partition into the lipid bilayer of cell membranes disrupting several vital functions. The present research was concerned with the effects that the chronic administration of PCP could produce in vivo to the sciatic nerve of rats. X-ray diffraction patterns obtained from freshly dissected and dried sciatic nerves of PCP treated rats did not show significant differences in their reflections with respect to those present in the patterns from untreated animals. However, morphological studies performed by optical and electron microscopy showed degenerative changes in about 10% of the A and B type of nerve fibers.

This study deals with the structural perturbations that the aminoglycoside antibiotic gentamicin (GENT) can produce to phospholipid bilayers. Two multibilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and the other of dimyristoylphosphatidylethanolamine (DMPE) were allowed to interact with GENT. The experiments were performed in both a hydrophobic and a hydrophilic medium below the phospholipid main transition tem­peratures. X-ray diffraction techniques were used to determine the extent of the perturbation induced by GENT. The maximum effect was attained when GENT interacted with DMPC in the hydrophobic medium. On the other hand, GENT in aqueous solutions was unable to per­turb in any significant extent the structure of the phospholipids under study.

Asocainol (ASOC) belongs to class I of the antiarrhytmic drugs, i.e., those that exert their action at the level of the sodium channels of the myocardial cell membrane. It has been suggested that their molecular mechanism of action might be through nonspecific interactions with phospholipids that surround the channel proteins. In order to test this hypothesis, ASOC was made to interact with two multibilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and the other of dimyristoylphosphatidylethanolamine (DMPE). These are the type of lipids that are respectively found in the outer and inner monolayers of human erythrocytes. The experiments were carried out in a hydrophobic as well as in a hydrophilic medium below the phospholipid main transition temperatures. The perturbing effect of ASOC upon the bilayer structures was determined by X-ray diffraction. It was found that ASOC was able to fluidize DMPC in both media but not to DMPE.

Several hypotheses link the molecular mechanism of action of the antiarrhythmic drugs (AAD) that belong to class I to non-specific interactions with phospholipids sited in the neighborhood of sodium channels in the membrane of the myocardium. Procainamide (PROC ), one of the least lipophilic drugs of this group, was induced to interact with bilayers of dimyristoylphosphatidylcholine (DMPC) and dimirystoylphosphatidylethanolamine (DMPE), liposomes of DMPC and human erythrocytes. The perturbing effects of PROC upon these systems were respectively determined by X-ray diffraction, fluorescence spectroscopy and scanning electron microscopy. It was found that PROC exerted very little effect upon DMPC and DMPE even at such a high concentration as 10 mᴍ . However, at therapeutical plasma concentrations, PROC induced shape changes in vitro to red cells.