Mechanistic aspects of the delay in the G2 phase of the cell cycle caused by tumor promoter 12-O-tetradecanoylphorbol-13-acetate in HeLa cells.
In order to gain an insight into the nature of the radiomimetic activity by which the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) alters cell cycle parameters in HeLa cells, possibilities of modifying the TPA-induced G2 block and recovery from it were studied. TPA-induced G2 blockage was analysed by counting mitotic figures. It was not influenced by hydroxyurea (10(-3) M) thus indicating that it is independent of DNA synthesis. TPA-induced decrease of mitotic activity occurred faster than that caused by cycloheximide (10(-5) M) indicating that the TPA-sensitive transition point in G2 is closer to mitosis than that for cycloheximide. Superoxide dismutase, catalase, alpha-tocopherol, the radioprotector S-(2-aminoethyl)isothiuroniumbromide.HBr (AET), caffeine and indomethacin and eicosatetraynoic acid (ETYA), both inhibitors of oxygenases in the arachidonic acid cascade, were not capable of reducing the TPA-induced G2 response. Under certain conditions small concentrations of AET (10(-8) M) and ETYA (10(-8) M) appeared to improve recovery slightly. Mannitol and sorbitol, however, both hydroxyl radical scavengers at 0.1 M concentration reduced TPA-effectiveness to a large degree (0.1 M D- and L-mannose were ineffective). Dimethylsulfoxide (0.1 M), another hydroxyl radical scavenger, was ineffective.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010704:Phorbols / Q000494:pharmacology*; D014176:Protein Biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D010704:Phorbols; D015117:5,8,11,14-Eicosatetraynoic Acid; D000338:beta-Aminoethyl Isothiourea; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate