Tumor Promoter Phorbol 12-myristate 13-acetate Induces a Clastogenic Factor in Human Lymphocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 79; no. 23; pp. 7509 - 7513
• Main Authors: Emerit, Ingrid, Cerutti, Peter A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01-12-1982; National Acad Sciences
• Subjects: Arachidonic Acids - metabolism; Blood; Bloom syndrome; Carcinogenesis; Cells, Cultured; Chromosome Aberrations; Culture media; Cyclooxygenase Inhibitors; Erythrocytes; Humans; Lymphocytes; Lymphocytes - drug effects; Molecular Weight; Mutagens - metabolism; Phorbols; Phorbols - pharmacology; Superoxide Dismutase; Superoxides; Tetradecanoylphorbol Acetate - pharmacology; Ungulates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.79.23.7509

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 (<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.