Tumor promoter phorbol 12-myristate 13-acetate induces a clastogenic factor in human lymphocytes.

Abstract

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 MW (< 10,000) clastogenic factor (CF) in phytohemagglutinin-stimulated human blood and lymphocyte cultures. Bovine erythrocyte Cu.sbd.Zn superoxide dismutase strongly inhibited PMA clastogenicity, the formation of CF and the action of previously formed CF. The nonsteroidal anti-inflammatroy agents indomethacin, imidazol and 5,8,11,14-icosatetraynoic acid inhibited PMA clastogenicity and the clastogenic activity of previously formed CF. Superoxide radicals and stimulation of the arachidonic acid cascade may 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.