Effects of retinoic acid and tumor promoter 12-o-tetradecanoylphorbol-13-acetate (TPA) on the cell cycle of HeLa cells.

The influence of retinoic acid (RA) - a modifier of tumor promotion - on the cell cycle of HeLa cells, and its ability to interfere with the early irradiation-like effects induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) has been investigated by a variety of different techniques. These include measurement of thymidine incorporation and uptake, of labelling and mitotic indices, and of DNA histograms by flow cytometry. Within 24 h RA (2 X 10-5 M) alone caused a short-lasting inhibition of DNA synthesis; later a decrease of cells in S phase and a steady descending mitotic activity were observed. On combined treatment with RA and TPA (10-8 M), the latter seems to dominate RA in two instances: (1) the transient G2 blockage due to TPA is seen as the earliest effect; however, the cultures do not seem to recover as well if RA is also present; (2) the TPA-induced GI blockage appears to be effective but less pronounced in the presence of both chemicals. Where the third typical TPA-induced effect is concerned, however, both compounds seem to act to a comparable degree in the same time frame; namely by an initial inhibition of DNA synthesis which thus might be a point of critical interference if promoter and modifier age given together.