Synergistic effect between antitubulin agents and cellular camp in stimulating dna synthesis by 3t3 cells

Incorporation of [3H]TdR into 3T3 cells stimulated by insulin and cholera toxin or 8Br-cAMP was markedly enhanced by colchicine, demecolcine, vinblastine or nocodazole. These antitubulin agents enhanced DNA synthesis in a dose-dependent manner. In the presence of colchicine and insulin, cholera toxin or 8Br-cAMP stimuleted DNA synthesis in a concentration-dependent fashion. When insulin was replaced by other growth factors, e. g. yasopressin, EGF. FDGF or PDGF, addition of colchicine also enbanced DNA synthesis stimulated by cholera toxin or 8Br-cAMP. The effect of colchicine on DNA synthesis was also demonstrated by increased autoradiographic labeling of nuclei. Our findings show that depolymerization of cytoplasmic microtubules acts synergistically with cAMP-elevating agents and peptide hormones to initiate DNA synthesis.