The anticancer drug cisplatin interacts with the human erythrocyte membrane

Drugs which exert their effects by interacting with DNA cause structural an d functional membrane alterations which may be essential for growth inhibit ion by these agents. This paper describes the interaction of cisplatin with the human erythrocyte membrane and models constituted by bilayers of dimyr istoylphosphatidylethanolamine (DMPE) and diacylphosphatidylserine (DAPS), representative of phospholipid classes located in the inner monolayer of th e erythrocyte;membrane, and of dimyristoylphosphatidylcholine (DMPC), a cla ss present in its outer monolayer. Cisplatin ability to perturb DMPE, DAPS and DMPC bilayer structures was determined by X-ray diffraction and fluores cence spectroscopy. Electron microscopy disclosed that human erythrocytes i ncubated with 35 mu M cisplatin., which is its therapeutical concentration in serum, developed cup-shaped forms (stomatocytes). According to the bilay er couple hypothesis, this means that the drug is inserted into the inner m onolayer of the erythrocyte membrane, a conclusion supported by the studies on model systems.