glutaminase and Carcinoma-256--Walker

Topics: Animals; Arginase; Asparaginase; Carcinoma 256, Walker; Carcinoma, Brown-Pearce; Carcinoma, Ehrlich Tumor; Carcinoma, Krebs 2; Chymotrypsin; Deoxyribonucleases; Enzyme Therapy; Glutaminase; Hyaluronoglucosaminidase; Leukemia, Experimental; Leukemia, Radiation-Induced; Lyases; Lymphoma, Non-Hodgkin; Mammary Neoplasms, Experimental; Mice; Neoplasms, Experimental; Pyridoxal Phosphate; Rats; Ribonucleases; Salts; Sarcoma, Avian; Sarcoma, Experimental; Trypsin; Vanadium

Melatonin is the main hormone involved in the neuroendocrine-immune axis. It also presents antitumour activity. To evaluate the role of melatonin on the progression of Walker-256 tumour in rats we determined the effect of the hormone on some biochemical and functional aspects of macrophage and lymphocytes from cachectic rats. An important finding observed in immune cells from tumour-bearing (TB) rats is the impairment on glutamine and glucose metabolism in such cells. These changes are very similar to those observed in pinealectomized rats (PNX). The increased production of lactate and the flux of glucose through the Krebs cycle and the reduction in glutamine consumption seems to be involved in the immunosuppression presented in the TB and PNX animals. Melatonin treatment restored the changes observed in the metabolism of glucose and glutamine and stimulated the proliferation of lymphocytes from tumour-bearing rats. The results indicate that the effect of melatonin upon tumour growth involves the stimulation of the immune system by the hormone.

Topics: Animals; Antioxidants; Carbon Dioxide; Carbon Radioisotopes; Carcinoma 256, Walker; Citrate (si)-Synthase; Citric Acid Cycle; Glucose; Glucosephosphate Dehydrogenase; Glutaminase; Glutamine; Hexokinase; Lymphocytes; Macrophages; Male; Melatonin; Pineal Gland; Rats; Rats, Wistar

It was previously shown that polyunsaturated and saturated fatty acid rich diets affected metabolic and functional changes in macrophages and a variety of immune tissues (thymus, mesenteric lymph nodes and spleen). This study reports metabolic and functional changes in peritoneal macrophages and lymphocytes of Walker-256 ascites cell tumour-bearing rats which were fed (a) normal balanced diet (3% fat), (b) diet enriched (15% fat) with polyunsaturated fatty acids or (c) diet fortified (15% fat) with saturated fatty acids. Neither of the fatty acid enriched diets affected macrophage migration following tumour cell implantation and ascitic cell growth. However both of these fortified fatty acid regimes enhanced the production of H2O2 by macrophages and lymphocytes. The maximum catalytic capacities of hexokinase, glutaminase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were measured in resident and tumour activated macrophages and lymphocytes obtained from rats fed the three fatty acid dietary regimes during seven days of tumour ascites cell growth. Tumour growth caused an increase in the activities of all of the above enzymes in macrophages irrespective of the fatty acid composition of the diet and notably decreased, independent of dietary fatty acid composition, the activities of the enzymes in lymphocytes. Only glutaminase activity in the lymphocytes of tumour bearing animals fed an unsaturated fatty acid-rich diet was not reduced, but was increased by 78%. Moreover macrophages from control rats fed an enriched polyunsaturated fatty acid diet had increased hexokinase activity (21%), decreased glutaminase (48%) and citrate synthase (decreased 41%) relative to the activities of these enzymes in macrophages of animals maintained on a balanced fatty acid diet. The feeding of both fatty acid rich diets did not modify the pattern of lymphocyte responses during the growth of tumour cells in these animals. None of the fatty acid diets modified the growth rate nor the yield of tumour cells in the peritoneal cavity.

Topics: Animals; Carbohydrate Metabolism; Carcinoma 256, Walker; Dietary Fats; Enzyme Activation; Glucosephosphate Dehydrogenase; Glutaminase; Glutamine; Glutathione Peroxidase; Hexokinase; Hydrogen Peroxide; Lymphocytes; Macrophages; Male; Malondialdehyde; Neoplasm Transplantation; Rats; Rats, Wistar

Key enzyme activities of glycolysis, pentosephosphate pathway, Krebs cycle, and glutaminolysis were measured in lymphocytes and macrophages of 3- and 15-month-old rats from the control, thioglycollate-injected, and Walker 256 tumor-implanted groups. The percentage of phagocytosis, phagocytic index, and production of H2O2 in macrophages and the rates of [2-14C]-thymidine and [5-3H]-uridine incorporation in cultured lymphocytes were also determined. The results indicate that the percentage of phagocytosis was not affected but the phagocytic index increased by twofold as a consequence of ageing, whereas the production of H2O2 reduced. The rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation in lymphocytes from aged rats were lower as compared to those of mature animals in the three groups. Taken as a whole, the results of enzyme activities suggest that ageing may reduce the capacity for glucose utilization in lymphocytes and macrophages under the three conditions. Lymphocyte and macrophage glutamine metabolism was not markedly affected by ageing. Therefore, an impaired glucose metabolism during ageing may be one important mechanism for the alteration in lymphocyte proliferation and macrophage phagocytosis observed and also for the modification of the response to inflammatory and tumor challenges.

Topics: Aging; Animals; Carcinoma 256, Walker; Citrate (si)-Synthase; Citric Acid Cycle; Energy Metabolism; Glucosephosphate Dehydrogenase; Glutaminase; Glutamine; Glycolysis; Hexokinase; Hydrogen Peroxide; Lymphocyte Activation; Lymphocytes; Macrophages; Male; Neoplasm Transplantation; Pentose Phosphate Pathway; Phagocytosis; Rats

1. The effect of age and Walker 256 tumor on maximal phosphate-dependent glutaminase activity of rat immune tissue was determined. Glutaminase is a key enzyme in the metabolism of glutamine, an important fuel for normal and neoplastic cells. 2. Maximal activity of phosphate-dependent glutaminase was measured in immune tissues and tumors of Walker 256 tumor-bearing young (28 days old), mature (3 months old) and aged (15 months old) Wistar rats. The following tissues were examined: thymus, spleen, mesenteric lymph nodes and tumor. 3. Tumor implantation for 14 days reduced glutaminase activity in the thymus and mesenteric lymph nodes. Tumor glutaminase activity was lowest in aged rats and highest in the mature group. 4. Comparison of glutaminase activity in immune and tumor tissues suggested the flux of glutamine between these tissues in the 3 groups. Glutaminase activity was 2.8-fold higher in immune tissues in aged rats (2.58 +/- 0.35 vs 0.93 +/- 0.16 mumol min-1 g tissue wet weight-1, mean +/- SEM, 5 rats), and 1.9- (4.14 +/- 0.47 vs 8.36 +/- 1.29 mumol min-1 g tissue wet weight-1, mean +/- SEM, 5 rats) and 2.5-fold increased (2.41 +/- 0.20 vs 5.92 +/- 0.22 mumol min-1 g tissue wet weight-1, mean +/- SEM, 5 rats) in tumor tissue in the mature and young groups, respectively. These results suggest the deviation of glutamine flux from defense cells to the neoplastic tissue in tumor-bearing young and mature rats and may partially explain the slow cancer growth in elderly patients.

Topics: Aging; Animals; Carcinoma 256, Walker; Glutaminase; Immunohistochemistry; Lymph Nodes; Male; Mesentery; Neoplasm Transplantation; Phosphates; Rats; Rats, Wistar; Spleen; Thymus Gland

Topics: Alcaligenes; Ammonia-Lyases; Animals; Asparaginase; Carboxypeptidases; Carcinoma; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Cell Line; Enzyme Therapy; Glutaminase; Humans; Leukemia, Experimental; Liver Neoplasms; Mice; Neoplasms; Neoplasms, Experimental; Sarcoma, Experimental

Topics: Adenocarcinoma; Adenoma; Animals; Carcinoma 256, Walker; Carcinoma, Squamous Cell; Fibrosarcoma; Glutaminase; Growth; Mammary Neoplasms, Experimental; Mathematics; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Osteosarcoma; Rats; Time Factors