Emerit I, Cerutti P A
Proc Natl Acad Sci U S A. 1982 Dec;79(23):7509-13. 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 (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.
研究了肿瘤促进剂佛波酯12 -肉豆蔻酸酯13 -乙酸酯（PMA）的致断裂作用机制，即诱导染色体畸变的能力。10和100 ng/ml的PMA在植物血凝素刺激的人血和淋巴细胞培养物中诱导形成低分子量（小于10,000）的致断裂因子（CF）。牛红细胞铜锌超氧化物歧化酶强烈抑制PMA的致断裂性，包括CF的形成和先前形成的CF的作用。非甾体抗炎药吲哚美辛、咪唑和5,8,11,14 -二十碳四炔酸抑制PMA的致断裂性和先前形成的CF的致断裂活性。这些结果表明，超氧自由基和花生四烯酸级联反应的激活在PMA诱导的致断裂性和CF的作用机制中起作用。CF可能将PMA与细胞膜的初始相互作用与基因组联系起来。
