Cytoskeleton-disrupting drugs enhance effect of growth factors and hormones on initiation of DNA synthesis.

Abstract
Addition of growth factors such as prostaglandin[PG]F2.alpha. or fibroblastic growth factor [FGF] to quiescent Swiss mouse 3T3 cells resulted in an abrupt increase in the rate of initiation of DNA synthesis after a lag phase of 13-15 h. This increase could be quantified by a rate constant k. Addition of colchicine, Colcemid or vinblastine had a synergistic effect on the initiation of DNA synthesis triggered by PGF2.alpha. or FGF by increasing the value of k. These drugs alone had no effect. Colchicine had a synergistic effect only if added within 8 h of the PGF2.alpha. or FGF addition. Colchicine exerted its full effect when it was present only for the first 5 h with either growth factor. An intact cytoskeleton is not required for the initiation of DNA synthesis. Furthermore, cytoskeleton-disrupting drugs enhance the stimulatory effect of the growth factors.