Differential stimulation of mononuclear phagocyte IL 1 production and oxidative burst by tumor-promoting and non-tumor-promoting agents.

Adherent bone marrow, spleen and peritoneal mouse macrophages, as well as human peripheral blood monocytes were exposed in vitro to the phorbol ester derivatives 12-O-tetradecanoyl-phorbol-13-acetate (TPA), phorbol 13-monoacetate (PA), phorbol 12-myristate (PM), phorbol 12,13-diacetate (PDA), phorbol 12,13 dibutyrate (PDBu), TPA-20 aldehyde (TPA-AL), phorbol 12-retinoate 13-acetate (PRA), 4-alpha TPA (alpha-TPA) and to mezerein (MEZ) and aplysiatoxin (APL). The triggered macrophages/monocytes were tested for the production of an IL 1-like activity by the thymocyte proliferation assay and for H2O2 generation in a quantitative method which is based on the H2O2-mediated and horseradish peroxidase-dependent oxidation of phenol red. The results showed that strong first stage and second stage tumor promoters such as TPA, PDBu, PRA, MEZ and APL are also strong stimulators of IL 1 and H2O2 generation, whereas weak tumor promoters exhibited a low, if any, effect at all. The afore-described findings lend support to the idea that chronic inflammatory phagocytes might play a role in the tumor promoting process by furnishing both carcinogenic and growth factors at the site of tumor origin.