EXPRESSION OF G(1) AND G(2) CYCLINS MEASURED IN INDIVIDUAL CELLS BY MULTIPARAMETER FLOW-CYTOMETRY - A NEW TOOL IN THE ANALYSIS OF THE CELL-CYCLE

Multivariate analysis of the expression of cyclin proteins and DNA content has opened new possibilities for the study of the cell cycle. By virtue of their cell cycle phase specificity, the expression of cyclins may serve, in addition to DNA content, as another marker of a cell's position in the cycle, and provide information about the proliferative potential of cell populations. Several applications of the methodology based on bivariate analysis of DNA content v. expression of B, E and D type cyclins are reviewed: 1 expression of cyclins by individual cells during their progression through the cycle can be studied, using exponentially growing cells without the necessity of cell synchronization or other perturbations of the cycle; 2 cells having the same DNA content but residing in different phases of the cycle (e.g. G(2) diploid v. G(1) tetraploid) can be distinguished; 3 cell transition from G(0) to G(1) and progression through G(1) (e.g. mitogen stimulated lymphocytes) can be assayed; 4 the population of proliferating cells can be distinguished from noncycling cells based on dual cell labelling with a G(1) and G(2) cyclin antibody; 5 cyclin restriction points can serve as additional cell cycle landmarks to map the point of action of antitumour drugs; 6 unscheduled expression of cyclins (e.g. the presence of cyclin B1 during G(1) and S) can be detected in several tumour transformed cell lines, possibly indicating disregulation of the machinery of cell cycle progression. The last finding 6 is of special importance, because such disregulation may be of prognostic consequence in human tumours.