Changes in the Lipid Composition of Biological Membranes under the Influence of Endogenous and Exogenous Factors.

Quantitative and qualitative assessments of cell membrane components are essential for the accurate interpretation of processes occurring in biological membranes. Changes in the structure and function of cell membrane components have been linked to oxidative stress. Oxidative stress induced by chronic ethanol consumption or cancer transformation has been implicated in changing the levels of phospholipids and fatty acids in the cell membrane. In this study, we used high-performance liquid chromatography to quantitate the effects of alcohol and malignant transformation on membrane components, namely phospholipids and free fatty acids. Ethanol increased the phospholipid levels. Moreover, the process of malignant transformation was accompanied by increased levels of phospholipids and arachidonic acid as well as decreased levels of linoleic acid and α-linolenic acid. Thus, these oxidative stress-inducing conditions that cause variations in the cellular composition affect the actions of the cell membrane and cell function.

Mechanisms of transport across cell membranes of complexes contained in antitumour drugs.

Various mechanism of antitumour drug transport across cell membranes has been described. Particular attention has been paid to a passive transport, active transport and multidrug resistance of complexes contained in antitumour drugs. A drug supply to the target site depends on the blood circulation within the tumour, on characteristic drug diffusion in the tissue, and also on binding protein. The physiologic transfer of hydrophilic compounds across the membrane is usually intermediated by means of a specific receptor or a carrier in that membrane, which facilitates the transport of compounds to and from the cell. Some drugs, e.g. doxorubicin and annamycin, can pass across the membrane by intermediacy of liposomes which exhibit a great activity in penetrating into tumour cells. The efficiency of antitumour drugs is limited by the appearance of resistance, i.e. by the lack of sensitivity of the cell to the administered drug. The presence in the membrane of specific proteins belonging to the ABC carriers group is postulated in a resistance theory; they would be responsible for 'pumping out' lipophilic drug molecules from the cell. Participation of high-energy ATP molecule is required by P-glycoprotein (Pgp) and by MRP protein described in this paper for their action. The mechanisms that are responsible for the cell resistance to drugs have been presented by analysing the resistance to antimetabolites, particularly to folate and fluoropyrimidine analogues, to alkylating agents, e.g. cisplatinum, and to heterocyclic compounds being responsible for so-called multidrug resistance.