Studies on the mechanism of action of proliferation inhibitory factor (PIF)

Preliminary studies on the mechanism of action of the proliferation inhibitory factor (PIF) are described. The proliferation inhibitory factor does not appear to alter the culture medium or to interfere with the growth-enhancing effect of serum. Inhibition of cellular proliferation is not absolute and can readily be reversed if the PIF is removed. There is a rapid attainment of the normal doubling time with a lag period of about 24 hr or less. A synchronized population of cells was utilized to show that all treated cells go through one cell division before the inhibitory effect is seen. Experiments designed to examine the effect of PIF at different times in the cell cycle demonstrated that the inhibitor was most effective when present during mitosis, and that treating cells during G1 had negligible effect.