Flow cytometric DNA histograms and type of growth.

Abstract

DNA histograms of human tumors should be interpreted together with the type of growth. In order to prove this connection the Ehrlich ascites tumors of 144 mice were investigated by absolute cell counting and flow cytometry. The exponential, transition and steady-state phases of tumor development were defined as types of growth based on the logistic function (Verhulst-Pearl). Flow-cytometric histograms (ethidium-bromide, olivomycin) were evaluated by two methods presupposing lognormal distribution and resulting in the same trend of changes concerning the percentage of cells in the three cell-cycle phases. In exponential growth the histograms show a high S-phase compartment and a decrease of the G2M peak. The increased percentage of S-phase cells is caused by a recruitment from G0-1 and G0-2 after transplantation. The decrease of the G2M peak is due to the exponential growth, a recruitment from G0-2 and a relative shortening of G2M duration. A high G2M peak and a low S-phase portion occur in steady state. Besides a decrease of DNA-synthesizing cells the S compartment decreases as a result of a relative S-phase shortening. For the increase of the G2M peak, transition into steady state, prolongation of G2M duration, recruitment of G0-1 and the occurrence of G0-2 cells are responsible. The same histogram may reflect different biological behavior patterns depending on the type of growth.