Radiomimetic activity of phorbol esters exerted in HeLa cells in comparison with their tumor-promoting capacity.
The biological activities exerted in mouse skin by three closely related phorbol esters were compared with the effects of these compounds on HeLa cells. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate has been shown previously to influence various cell cycle parameters of these cells, thereby mimicking X-irradiation [Kinzel, V., Richards, J., and Stöhr, M. Science (Wash. D. C.), 210: 429-431, 1980]. Qualitatively similar effects were exerted by the mitogenic and irritant but almost nonpromoting "incomplete" phorbol esters 12-O-tetradeca-2-cis-4-trans-6,8-tetraenoylphorbol-13-acetate and 12-O-retinoylphorbol-13-acetate. Cell cycle parameters were analyzed by measuring thymidine incorporation rates, labeling indices, DNA histograms gained through flow cytometry, and mitotic activity. In every case, 12-O-tetradecanoylphorbol-13-acetate was more effective than 12-O-tetradeca-2-cis-4-trans-6,8-tetraenoylphorbol-13-acetate or 12-O-retinoylphorbol-13-acetate. The analysis of the influence of phorbol esters in G2 phase showed that, in order to reach the effectiveness of 10(-8) M 12-O-tetradecanoylphorbol-13-acetate, approximately 10 times the concentration of either 12-O-tetradeca-2-cis-4-trans-6,8-tetraenoylphorbol-13-acetate or 12-O-retinoylphorbol-13-acetate has to be applied. Therefore, the susceptibility of replicating HeLa cells to these phorbol derivatives reflects the promoting rather than the mitogenic and irritant capacity of these compounds.
D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010703:Phorbol Esters / Q000633:toxicity*; D010704:Phorbols / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D010703:Phorbol Esters; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate