TI: Antitumor Effects of Hydrogen Peroxide in vivo. DT: July 9, 1981 AU: C.F. Nathan and Z.A. Cohn SO: J. Exp. Med, Vol. 154, November 1981, pp 1539-1553 AB: Hydrogen peroxide, a secretory product of mononuclear phagocytes, accounts for a considerable portion of their nonphagocytic lysis of tumor cells in at least three circumstances: when certain secretagogues are added, when antitumor antibody is present, or when the tumor cells are coated with eosinophil peroxidase. Granulocytes also secrete H2O2, which may participate in their cytotoxic effects in a variety of situations. Finally, preformed or enzymatically generated H2O2, with or without a peroxidase, lyses tumor cells. In the present study we sought to devise a nontoxic way to deliver hydrogen peroxide to sites of malignancy in vivo and to test its antitumor efficacy. Glucose oxidase was chosen for this purpose because its substrates, glucose and oxygen, are abundant in the body fluids, because its sole products are H2O2 and gluconic acid, and because a flux of H2O2 generated enzymatically in situ might be less toxic than injection of preformed H2O2. To prolong the retention of the H2O2 generating system at the site of administration, glucose oxidase was coupled covalently to polystyrene microspheres. Below are described the distribution of parenterally injected glucose oxidase-latex particles (GOL), their antitumor effect in the peritoneal cavity and subcutaneous tissues of the mouse, the role of supplemental oxygen, the synergy between GOL and another antitumor agent capable of inhibiting a major peroxide-catabolizing pathway in tumor cells, and the relative lack of toxicity of this novel treatment.