© 1985 Oxford University Press
research-article |
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
German Cancer Research Center, Institutes of Experimental Pathology D-6900 Heidelberg, FRG
1Biochemistry, Im Neuenheimer Feld 280 D-6900 Heidelberg, FRG
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, 
-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.