Interaction of two hormones and their effect on observed rate of initiation of DNA synthesis in 3T3 cells

Abstract

THE rate of replication of mammalian cells changes in response to alterations in the external environment usually by expansion or contraction of the average time of the G₁ phase of the cell cycle; the remaining phases are relatively constant (S, G₂, M)^1–3. Thus, when varying concentrations of serum⁴ or the growth-promoting^5–7 factors are added to relatively quiescent fibroblastic cells variations in rates of cell division are mainly due to differences in rates of initiation of DNA synthesis^4,6. Recently Brooks⁸ has shown that addition of serum and adenosine to quiescent BHK fibroblasts stimulated the cells to enter S phase with first-order kinetics, although without adenosine the kinetics were more complicated. We now report that the stimulation of DNA synthesis induced by prostaglandin F_2α (PGF_2α) can be described as an increase in a first-order rate constant for exit from the G₁ phase preceded by a lag phase of relatively fixed duration. Insulin and certain nutrients which increase the effect of PGF_2α upon DNA synthesis do so by changing the same rate constant.