Tumor promoters stimulate hyperplasia of microtubule organizing center and inhibit DNA synthesis in cultured cells.

Abstract

Chemical tumor promoters induce significant morphologic changes in several cultured cell models. In this article we describe a new effect of two potent, chemically different tumor promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA) and dihydroteleocidin B (DHTB) on cultured human HeLa and melanoma cells. Using immunofluorescence microscopy, we observed that TPA and DHTB induced a dramatic increase in the size (greater than or equal to 3X normal diameter) of the centrosome, a microtubule-organizing center, within 24 h of incubation. In HeLa cells the effect was serum- and dose-dependent, was observed in 76-92% of cells within 72 h of incubation, and was associated with an increase in cytoplasm-nucleus ratio and proliferation of microtubules from the centrosome. The tumor promoters inhibited serum-induced DNA synthesis in both cell lines. Electron microscopy revealed the presence of clumps of microcentriole bodies or fragments adjacent to the intact centriole.