Antitumor activity of an immobilized peroxidase system against murine Ehrlich ascites is mediated by the immune system.
Earlier studies have shown that a mixture of glucose oxidase and a peroxidase exerts a tumoricidal effect on rats bearing Novikoff hepatomas when the enzyme mixture is injected intraperitoneally. The enzyme mixture was shown to be nontoxic when injected into healthy animals at levels up to 600 times the therapeutic dose. In the present study, we have evaluated the possibility that the host immune defense system may be involved in the antitumor activity of the peroxidase system, using the murine Ehrlich ascites tumor as the target. The results revealed that the antitumor activity of the peroxidase system is absent in tumor-bearing animals whose immune system has been compromised by whole body gamma-irradiation or by an induced selenium deficiency. The peroxidase system was also found to be inactive in tumor-bearing mice whose immune system was suppressed by the administration of cyclosporin A as well as in athymic (nu/nu) mice. These results indicate that T lymphocytes may directly or indirectly be involved in the in vivo antitumor activity of the peroxidase system. This could explain the observed high selectivity toward tumor cells by the enzyme system in vivo and its lack of toxicity in healthy animals.
Combs
S H
SH
Department of Biochemistry and Molecular Biology, Texas Tech University Health Sciences Center, Lubbock 79430.
Morgan
C D
CD
Everse
J
J
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000628:therapy*; D016572:Cyclosporine / Q000494:pharmacology; D004800:Enzymes, Immobilized / Q000627:therapeutic use*; D005949:Glucose Oxidase / Q000008:administration & dosage*; D006735:Horseradish Peroxidase / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012643:Selenium / Q000172:deficiency; D014916:Whole-Body Irradiation
D004800:Enzymes, Immobilized; D016572:Cyclosporine; D005949:Glucose Oxidase; D006735:Horseradish Peroxidase; D012643:Selenium