Copper, Ceruloplasmin, and Superoxide Dismutase in Tumor Bearing Mice

Abstract Investigation on the immunoprotective activity of Cu/Zn superoxide dismutase from Humicola lutea 103 AL (HLSOD) in hamsters with transplanted myeloid tumor was performed. Survivability, tumor growth and tumor transplantability were followed. The immune status of tumor-bearing animals, injected with the optimal protective HLSOD dose, was examined during 27 days after tumor transplantation by the following parameters: (i) the number, migration and phagocytic activity of peritoneal macrophages, (ii) the phagocytic activity of blood polymorphonuclear leukocytes (PMNs), (iii) the responsibility in vitro of spleen lymphocytes to T and B cell mitogens. It was established that intraperitoneal inoculation of HLSOD produced a protective effect on the development of tumors. Elongation of the latent time for tumor appearance and inhibition of the tumor growth were observed. The decreased percentage of mortality in early stage of tumor progression was established. Immunological studies on tumor-bearing hamsters (TBH) induced a tem porary immunorestoring effect on the suppressed phagocytic activities of peritoneal macrophages and blood PMNs during the first 14 days of tumor development. Moreover, HLSOD showed an expressed stimulating effect on proliferative activity in vitro of spleen B lymphocytes from healthy and TBH as well. The immunorestoring and protective effect of the enzyme was probably due to improve of the oxidant-antioxidant balance in peritoneal phagocytes. The tem porary character of the effect can be explained with the interference of immunosuppressing factors produced by tumor tissue as well as by the presence of tumor antigens, tumor cells and antigen-antibody complexes in the circulation.

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Effect of Cu/Zn-Superoxide Dismutase from the Fungal Strain Humicola lutea 103 on Antioxidant Defense of Graffi Tumor-Bearing Hamsters

Zeitschrift für Naturforschung C ◽

10.1515/znc-2002-1-232 ◽

2002 ◽

Vol 57 (1-2) ◽

pp. 197-204 ◽

Cited By ~ 1

Author(s):

Emilia Ivanova ◽

Maria Angelova ◽

Ludmila Slokoska ◽

Svetlana Pashova ◽

Reneta Toshkova ◽

...

Keyword(s):

Superoxide Dismutase ◽

Tumor Growth ◽

Tumor Progression ◽

Catalase Activity ◽

Early Stage ◽

Fungal Strain ◽

Sod Activity ◽

Tumor Bearing ◽

Low Levels ◽

Humicola Lutea

A novel Cu/Zn-containing superoxide dismutase (SOD) was isolated from the fungal strain Humicola lutea 103. Previously, a protective effect of this enzyme (HLSOD) against tumor growth and also superoxide production in Graffi tumor-bearing hamsters (TBH) were established. The aim of the present study was to investigate the effect of HLSOD on the activity of endogenous SOD and catalase in the cells from TBH during tumor progression. Our results point out that transplantation of Graffi tumor causes a significant decrease in SOD activity in the cells from liver of the hosts (from 35 to 59% compared to the control). In the tumor cells relatively low levels of SOD (about 7 U mg protein-1) were found, and Cu/ZnSOD was the main isoenzyme in total SOD activity. Tumor growth resulted in a reduction of catalase activity, which correlated with the process of tumor progression. A single dose (65 U) treatment with HLSOD caused an increase in endogenous SOD and catalase activity in healthy animals and resulted in restoration of the antioxidant ability in liver cells of the hosts at the early stage of tumor progression. The results show the possible participation of HLSOD in the host oxidant-antioxidant balance, which is probably one of the factors of its immunoprotective action established earlier.

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Effect of a Fungal Cu/Zn Superoxide Dismutase on the Cell-Mediated Immune Response in Graffi Tumor Bearing Hamsters

Zeitschrift für Naturforschung C ◽

10.1515/znc-2003-1-222 ◽

2003 ◽

Vol 58 (1-2) ◽

pp. 128-134

Author(s):

Reneta Toshkova ◽

Emilia Ivanova ◽

Maria Angelova ◽

Pavlina Dolashka ◽

Wolfgang Voelter

Keyword(s):

Immune Response ◽

Superoxide Dismutase ◽

Tumor Progression ◽

Tumor Cells ◽

Leukocyte Adherence ◽

Tumor Bearing ◽

Cell Mediated Immune Response ◽

Leukocyte Adherence Inhibition ◽

Spleen Lymphocytes ◽

Adherence Inhibition

The antibody-dependent cell cytotoxicity (ADCC) of spleen lymphocytes, isolated fromhamsters with progressing myeloid Graffi tumor, was studied. The effect of the application of Cu/Zn superoxide dismutase, isolated from the fungal strain Humicola lutea (HL SOD), before and during tumor transplantation on the lymphocyte ADCC was examined. Myeloid Graffi tumor cells as target cells were used. Antibodies from a rabbit hyper-immune anti-tumor Graffi cells serum, or from tumor-bearing hamsters serum were used in the test. The leukocyte adherence inhibition (LAI) in the presence of tumor antigenwas examined also during tumor progression. ADCC of the spleen lymphocytes, determined by both, rabbit and hamster anti-tumor antibodies, decreased during tumor progression. The optimum treatment of the animals by HL SOD induced a 20-30% increase of lymphocyte cytotoxicity againstmyeloid Graffi tumor cells. Cytotoxicity in presence of tumor bearing hamsters serum was twofold lower as compared to that one determined in the presence of rabbit hyper-immune anti-myeloid Graffi tumor cells serum. Leukocyte adherence inhibition (LAI) index in the presence of tumor antigen increased during tumor development in the groups of treated and untreated animals. The LAI indices of HL SOD-treated tumor-bearing hamsters were lower than that of untreated animals with tumors, what can be explained by a higher adherence ability of leukocytes induced by HL SOD treatment (in formula for calculation of LAI index the adherence value is in the denominator). The results show the beneficial effect of HL SOD on the cell- mediated immune response of myeloid Graffi tumor bearing hamsters, what is probably due to the participation of the enzyme in the host’s oxidant-antioxidant balance

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