Oxidative Burst-Dependent Tumoricidal and Tumorostatic Activities of Paraffin Oil-Elicited Mouse Macrophages

Abstract

Mouse peritoneal macrophages (MPM) from C57BL/-6J, BALB/c, A strains, and (BALB/c♀ × C57BL/6J♂)F₁ offspring were treated with the oxidative burst (OB)-stimulant 12-O-tetra-decanoylphorbol 13-acetate, and their in vitro tumoricidal, tumorostatic, and OB activities were examined. Paraffin oil-elicited, but not thioglycollate (TG)-elicited, MPM exhibited cytotoxicity only toward Yac-1 cells and cytostatic activity toward Yac-1, EL 4, RBL-5, and RL♂ lymphoma cells. This activity was in correlation with the reduced capacity of TG-elicited cells to generate OB products. The toxic effect of such activated MPM was partially inhibited by catalase, superoxide dismutase, cytochrome c, and vitamin E (α-tocopherol) and was augmented by horseradish peroxidase and the catalase inhibitor aminotriazole (3-amino-1H-1,2,4-triazole), thus indicating the involvement of oxygen-derived toxic reagents, mainly hydrogen peroxide, in the MPM-mediated damage inflicted on the tumor cells. EL 4 cells incubated with nonstimulated MPM exhibited enhanced growth both in vitro and in vivo, whereas OB-stimulated MPM inhibited the growth of such cells in the same experimental systems.