Initiation of DNA synthesis by microtubule disruption in quiescent rat 3Y1 cells.

Abstract

Disruption of cytoplasmic microtubules by colchicine, colcemid or vinblastine induced the initiation of DNA synthesis and cell division in quiescent cultures of rat embryo fibroblast cell line, 3Y1, in the absence of growth factors. The microtubule-disruption-induced DNA synthesis was so marked that we could initiate analysis of the mechanism. Incubation of quiescent 3Y1 cells with high concentrations of vinblastine or those of vinblastine plus colcemid, which formed large tubulin paracrystals concomitant with the depolymerization of cytoplasmic microtubules, initiated DNA synthesis in the cells. Because these treatments did not increase the free tubulin level in the cells, but rather decreased it, an increase in the free tubulin level may not be required for initiation of DNA synthesis induced by microtubule-disrupting agents. Culture fluid of the 3Y1 cells incubated with colchicine did not stimulate the initiation of DNA synthesis when added to other quiescent 3Y1 cells after conversion of the colchicine in the culture fluid to lumicolchicine by ultraviolet irradiation. This suggested that colchicine treatment did not induce secretion of any mitogenic factors from 3Y1 cells. These results suggest that disruption of normal microtubules may elicit intracellular signals leading to cell proliferation.