Effect of tumour promoters on poly ADP-ribosylation in human epidermoid carcinoma HeP2 cells.
The present work was undertaken with the basic objective to compare the effect of related tumour promoters phorbol-12-myristate-13-acetate (PMA), benzoyl peroxide (BP) and mezerein (M) on poly ADP-ribosylation in HeP2 cells. PMA, BP and mezerein showed an increase in the enzyme activity to the extent of 66, 89 and 35% respectively. This was accompanied by a drop in NAD levels of 22% with PMA, 24% with BP and 49% with mezerein, PMA-treated cells showed a decrease in the enzyme activity of 42% with superoxide dismutase (SOD) and catalase (CAT), 18% with butylated hydroxy toluene (BHT), 52% with indomethacin and 32% with 3-aminobenzamine (3AB). However, for BP the inhibition was 16% with CAT, 41% with SOD, 18% with BHT, 34% with 3AB and there was no inhibition with indomethacin. The involvement of active oxygen species was supported by a 2.5-fold increase in superoxide anion levels with PMA and BP and no change with mezerein. There was a twofold and a 2.5-fold increase in Ca2+ influx after PMA and BP treatment respectively. It is concluded that PMA and BP mediate their effect on poly ADP-ribosylation through active oxygen species which in turn stimulates the influx of Ca2+ into cells and this may play an important role in signal transduction.
Singh
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Department of Biochemistry, AIIMS, New Delhi, India.
D001585:Benzoyl Peroxide / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D004224:Diterpenes; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009243:NAD / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000201:enzymology
D002273:Carcinogens; D004224:Diterpenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013729:Terpenes; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; C011309:mezerein; D011065:Poly(ADP-ribose) Polymerases; D013755:Tetradecanoylphorbol Acetate; D001585:Benzoyl Peroxide