Macrophage oxidative burst and related cytotoxicity. I. Differential activation by tumor-promoting and non-tumor-promoting phorbol esters.

Mouse peritoneal macrophages elicit an oxidative burst (OB) response upon stimulation with the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA). In this study we compare the OB-stimulating capacity of phorbol ester derivatives, structurally related to TPA, which differ in their tumor-promoting activity. Non-tumor-promoting derivatives such as phorbol 13-acetate, phorbol 12-myristate, TPA-20-aldehyde and 4-O-methyl TPA were tested. These reagents stimulate macrophages to generate OB products such as O-2 and H2O2, yet the amounts required for stimulation are 1,000 times higher than the amounts of TPA required to elicit a comparable response. It has also been observed that, in the same order of magnitude, the above-mentioned derivatives are less efficient than TPA in rendering macrophages cytolytic toward erythrocytes. Another strong tumor promoter tested, teleocidin, has been found to be as potent as TPA in the activation of macrophage OB and in related activities.