Use of Cell Culture in Pharmacology

During the last 15 years, cultures of cells in vitro, because of the intro­ duction of quantitative methods of high precision, have become a valuable tool for studies of the effects of certain classes of pharmacological agents. Cell cultures offer the possibility of observing the effects of drugs on cells in an artificial environment, without interference by nervous and hutnoral factors present in the intact organism. Furthermore, because during prepa­ ration of primary cultures the cells are released from the three-dimensional framework of tissue architecture, the influence of intercellular contact is greatly decreased or completely abolished. Cell systems thus permit an analysis of the responses of isolated cells to pharmacological agents. In this review, various applications of cell methods to the analysis of the mode of action of drugs are discussed. The action of certain drugs is characterized by a high specificity, and inhibition of a single process within the cultured cells is observed. Such specific inhibitors have become exten­ sively used in analyzing the role of various processes in cellular activities. This use of pharmacology in cell culture will, however, not be considered. After a primary of dispersed cells has been prepared from a piece of tissue by mechanical disruption or by the application of a suitable enzyme such as trypsin, in most cases only a small proportion of the cell population is capable of proliferation. Furthermore, under conditions in vitro the cells usually undergo marked changes of their metabolic activities. Even a primary culture, therefore, cannot be regarded as representative of the tissue of origin. Under cell conditions, in general a selection of cell types capable of continued proliferation takes place. In contrast to the situation in the intact organism, cell multiplication in vitro is not limited by growth-regulating mechanisms. Cells in prolonged culture, therefore, are, in some respects, comparable to mUltiplying microorganisms. Genetically pure cell populations may be obtained by of isolated cells. Normal human cells in usually retain their diploid chromosome set. They appear, however, to be limited in their proliferative capacity to a number of -ap­ proximately 60 cell divisions and then undergo degenerative changes which