Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity

The present study examined the ability of human monocytes to produce reacti ve oxygen intermediates after a contact with tumour cells. Monocytes genera ted oxygen radicals, as measured by luminol-enhanced chemiluminescence and superoxide anion production, after stimulation with the tumour, but not wit h untransformed, cells. The use of specific oxygen radical scavengers and i nhibitors, superoxide dismutase, catalase, dimethyl sulphoxide and deferoxa mine as well as the myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide , indicated that chemiluminescence was dependent on the production of super oxide anion and hydroxyl radical and the presence of myeloperoxidase. The t umour cell-induced chemiluminescent response of monocytes showed different kinetics from that seen after activation of monocytes with phorbol ester. T hese results indicate that human monocytes can be directly stimulated by tu mour cells for reactive oxygen intermediate production. Spontaneous monocyt e-mediated cytotoxicity towards cancer cells was inhibited by superoxide di smutase, catalase, deferoxamine and hydrazide, implicating the role of supe roxide anion, hydrogen peroxide, hydroxyl radical and hypohalite, We wish t o suggest that so-called 'spontaneous' tumoricidal capacity of freshly isol ated human monocytes may in fact be an inducible event associated with gene ration of reactive oxygen intermediates and perhaps other toxic mediators, resulting from a contact of monocytes with tumour cells.