The effect of insulin on the growth of transplanted tumors in mice

The growth of four murine transplantable tumours, Ehrlich ascites or solid tumour, an aplastic carcinoma, B-16 melanoma, and a thymoma, were suppressed in mice treated daily with insulin (2 IU). Since insulin increased the number of plaque-forming cells and the phagocytic activity of the liver and spleen cells, the retardation of the tumour growth was ascribed to immunological mechanisms.     

Effect of thermal environment upon transplanted tumors and growth of mice.

Ehrlich ascites tumor cells were inoculated subcutaneously in the dorsal, interscapular region of three groups of mice that were subsequently maintained in normo-, hypo- or hyperthermic environments. The controls, mice that had homologous whole spleens or thymic glands implanted in the same location, were maintained in a normothermic environment. Number of tumors established, their weights and volumes, and weights of animals were compared as well as tumor temperature, which was compared to brown fat and core temperatures.(1) The percentage of animals developing tumors was independent of environment. (2) Mice with tumors, and mice in which tumors did not take, gained more weight at the normothermic temperatures (21 °C) than at either 31 or 5 °C. (3). When the weight and volume of tumors are expressed per gram of mouse body weight, there is no difference between the hypo- and normothermic environments, but the weights and volume of tumors in a hyperthermic environment are only 36 and 58% respectively of the tumors in normothermic animals. (4) Tumor temperatures are about 1 °C cooler than the underlying brown fat regardless of environment, and brown fat was 0.5 °C cooler than the core temperature. (5) Transplanted thymus glands and spleens become encysted after 31 days; they proved to be cooler than the malignant tumors.     

Hematopoietic tissue reactions associated with the growth of syngeneic transplanted tumors in mice]

Hemangiopericytoma growth in syngeneic male mice F1 (CBA X C57BL/bj) led to regular hemopoietic changes: an increase in the spleen weight, spleen cell count, in the number of colony-forming units (CFU). It also induced augmentation of myelopoiesis in the spleen and leukocytosis with a sharp increase of segmented granulocytes in the circulating blood characterized as the "leukemoid reaction" syndrome. The latter occurred even when the tumour cells were transplanted into the splenectomized host. Although less marked, this leukemoid reaction was also noted in advanced hepatoma transplanted to syngeneic male mice F1 (CBA X C57BL/6j). No leukemoid reaction was observed in these mice after grafting syngeneic strain of urinary bladder carcinoma.     

Metabolic properties of erythrocytes of normal and genetically anemic mice

The murine hemolytic anemias microcytosis (gene symbol mk), normoblastosis (nb), spherocytosis (sph), and hemolytic (ha) are inherited as autosomal recessive diseases and resemble the human hereditary hemolytic anemias caused by defective enzyme activities in erythrocytes. The activities of 14 different enzymes of the glycolytic and pentose phosphate pathways were compared in erythrocytes from normal and anemic mice, but no quantitative differences suggesting enzyme deficiency were found. There were no major changes in reduced glutathione, NAD, NADP, or methemoglobin content. The rate of entry of glucose into the glycolytic and hexose monophosphate shunt pathways of intact erythrocytes was higher in mk/mk erythrocytes than predicted. Interpretation of studies of erythrocytes from anemic mice is generally complicated by the extremely high reticulocyte and nucleated cell counts in ha/ha, sph/sph, and nb/nb mice.Investigations in Kentucky (Dr. Hutton) were supported by Research Career Development Award 1-K4-AM-70, 186-01 and NIH Research Grant AM 16013-01 from the National Institute of Arthritis and Metabolic Diseases, and those at The Jackson Laboratory (Dr. Bernstein) by NIH Research Grant HD-00254 from the National Institute of Child Health and Human Development, by U.S. Atomic Energy Commission Contract AT(30-1)-1800, and in part by the George W. Perkins Memorial Fund and by income from the Endowment Funds of The Jackson Laboratory. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

The purine metabolism of human erythrocytes

This review summarizes currently available information about a crucial part of erythrocyte metabolism, that is, purine nucleotide conversions and their relationships with other conversion pathways. We describe the cellular resynthesis, interconversion, and degradation of purine compounds, and also the regulatory mechanisms in the conversion pathways. We also mention purine metabolism disorders and their clinical consequences. The literature is fragmentary because studies have concentrated only on selected aspects of purine metabolism; hence the need for a synthetic approach. Published in Russian in Biokhimiya, 2006, Vol. 71, No. 5, pp. 581–591.     

Altered purine and pyrimidine metabolism in erythrocytes with purine nucleoside phosphorylase deficiency

Purine and pyrimidine metabolism was compared in erythrocytes from three patients from two families with purine nucleoside phosphorylase deficiency and T-cell immunodeficiency, one heterozygote subject for this enzyme deficiency, one patient with a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, and two normal subjects. The erythrocytes from the heterozygote subject were indistinguishable from the normal erythrocytes. The purine nucleoside phosphorylase deficient erythrocytes had a block in the conversion of inosine to hypoxanthine. The erythrocytes with 0.07% of normal purine nucleoside phosphorylase activity resembled erythrocytes with hypoxanthine-guanine phosphoribosyltransferase deficiency by having an elevated intracellular concentration of PP-ribose-P, increased synthesis of PP-ribose-P, and an elevated rate of carbon dioxide release from orotic acid during its conversion to UMP. Two hypotheses to account for the associated immunodeficiency—that the enzyme deficiency leads to a block of PP-ribose-P synthesis or inhibition of pyrimidine synthesis—could not be supported by observations in erythrocytes from both enzyme-deficient families.This work was supported by U.S. Public Health Service Grant AM 19674 and 5 M01 RR 42 and by a Grant-In-Aid from American Heart Association (77-849) and with funds contributed in part by the Michigan Heart Association. N.L.E. is a Rheumatology Fellow from the Rackman Arthritis Research Unit supported by Training Grant USPHS AM 07080.     

Patterns of purine nucleotides in fish erythrocytes.

1. The purine nucleotides were determined in the whole blood of 9 fresh water teleosts and 2 marine selachians. 2. GTP and ATP accounted for 88-99% of the total erythrocytes purines. 3. The ATP/ADP ratio ranged from 11 to 60 in the erythrocytes of the fish examined. 4. GTP is widely distributed in fish erythrocytes but its level ranged from 1 to 33 nmol/mg Hb (0.4 to 9 mumol/ml erythrocyte). 5. Lepomis and Esox exhibited a GTP/ATP ratio as elevated as in Anguilla; moreover the concentration of GTP per mol of Hb (physiologically most indicative) is higher in Lepomis, Esox, Ictalurus and Silurus than in Anguilla.     

Lactate dehydrogenase and Krebs cycle enzyme activity in rat liver during the growth of transplanted and spontaneous tumors

Certain distinctions in the mouse and rat liver responses to transplanted and spontaneous tumours have been discovered at the initial periods of their growth. The most pronounced changes (the mosaic distribution of enzymatic activity in the lobe) are observed in the case of spontaneous tumours. Activities the Krebs cycle enzymes, especially of NAD-dependent enzymes are seen inhibited in the tumour-bearing liver at the terminal periods of growth of both spontaneous and transplanted tumours; lactate dehydrogenase activity increases (with the exception of mitochondrial lactate dehydrogenase in the rat liver with transplanted sarcomas).     

The effect of irradiation on the growth of human laryngeal tumors transplanted under the kidney capsule of immunocompetent mice

A study was made of the influence of gamma-radiation on the growth of human larynx squamous cell carcinoma transplanted under the capsule of the kidney of immunocompetent mice. The transplants were shown to increase in size 6 days after transplantation. Irradiation of animals 24 h after transplantation inhibited considerably the tumor growth. However, the preirradiation (24 h before operation) inhibited the growth of nonirradiated transplants to the same extent as the exposure of mice with the transplanted tumor fragments did: the radiation dose that induced 50% inhibition of the growth was 4.5 Gy and 5.3 Gy, respectively. Preliminary data indicate that tumor fragment of patients with the unfavourable prognosis increase in size and respond to radiation to a lesser extent.     

Effect of chemo- and radiotherapy on the growth of human strains of respiratory and excretory organ tumors transplanted in athymic mice

The effect of single and five-fold administration of 12 chemotherapeutic drugs on human strains of larynx, lung and kidney cancers and Wilms' tumor transplanted in nude mice was studied. Wilms' tumor was found to be more responsive to dactinomycin and cyclophosphamide. Larynx, lung and kidney cancers were resistant to all the chemotherapeutic drugs studied. The effect of irradiation of larynx cancer which resulted in short-term tumor growth retardation was also studied.     

Metabolic changes of lymphocytes and neoplastic cells in mice with Ehrlich ascites carcinoma during tumor growth

Changes in the activities of NAD⁺-and NADP-dependent dehydrogenases of lymphocytes and tumor cells were studied in mice with Ehrlich ascites carcinoma, as well as changes in the concentrations of oxaloacetate, lactate, and NAD⁺ in the course of tumor growth. During the major period of tumor growth, conditions are produced in the lymphocytes for increased intensity of aerobic reactions directed at energy reproduction combined with a somewhat decreased intensity of synthetic processes. In the tumor cells, conditions predominantly arise for intensification of plastic metabolic reactions and reactions related to anaerobic energy reproduction.