Tumor promoter phorbol 12-myristate 13-acetate induces a clastogenic factor in human lymphocytes.
The mechanism of the clastogenic action--i.e., the ability to induce chromosomal aberrations--of the tumor promoter phorbol 12-myristate 13-acetate (PMA) was investigated. PMA at 10 and 100 ng/ml induced the formation of a low molecular weight (less than 10,000) clastogenic factor (CF) in phytohemagglutinin-stimulated human blood and lymphocyte cultures. Bovine erythrocyte Cu-Zn superoxide dismutase strongly inhibited PMA clastogenicity, both the formation of CF and the action of previously formed CF. The nonsteroidal anti-inflammatory agents indomethacin, imidazol, and 5,8,11,14-icosatetraynoic acid inhibited PMA clastogenicity and the clastogenic activity of previously formed CF. These results suggest that superoxide radicals and stimulation of the arachidonic acid cascade play a role in PMA-induced clastogenicity and the mechanism of action of the CF. The CF may relate the initial interaction of PMA with the cell membrane to the genome.
D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D016861:Cyclooxygenase Inhibitors; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008970:Molecular Weight; D009153:Mutagens / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D009153:Mutagens; D010704:Phorbols; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate