Antiproliferative effects of 4′, 5′-unsaturated adenine nucleosides on leukemia L 1210 cells in vitro

Summary Several 4, 5-unsaturated adenine nucleosides were shown to have antiproliferative activity against L 1210 leukemia cells in vitro. The active nucleosides were cytotoxic to the L 1210 cells as demonstrated by Trypan Blue uptake. The cytotoxicity was not induced by alterations in the ribonucleoside and deoxyribonucleoside triphosphate levels of the L 1210 cells.     

Agglutination of leukemic cells and daunomycin entrapped erythrocytes with lectin in vitro and in vivo

Wheat germ agglutinin (WGA) agglutinated the L1210 leukemic cells and daunomycin entrapped erythrocytes in vitro. Comparing with control preparations, the greatest increase in survival was obtained in vivo when the daunomycin entrapped erythrocytes and WGA were given to BDF1 mice bearing L1210 cells.     

Antiinflammatory reaction associated with murine L1210 leukemia

Summary Mice bearing L1210 leukemia did not show impaired humoral or cellular immune response to antigenic stimulation during the early stage of the tumor, and a depressed response was noted only in the terminal stage. L1210 cells were shown to suppress inflammatory reaction in vivo.Supported in part by USPHS research grant No.5-01-RR05-352-12, and by theIndependent Order of Foresters, San Bernardino District 3208. We acknowledge the valuable assistance ofJudith Johnson andJames Tan in this project. Histopathological examination byDick H. Koobs is appreciated.     

Resolution of small G1 and G2 populations of L1210 leukemia by flow microfluorometric analysis aided by velocity sedimentation

L1210 leukemic cells grown in vitro were subjected to kinetic analysis using a flow microfluorometer. A single broad peak was found for the DNA content distribution if unfractionated cells were used; prior fractionation using lg velocity sedimentation allowed the separation of small peaks with smaller (G1) and larger (G2) DNA contents from the dominant S phase peak with intermediate DNA content.     

Aragusterol C: A novel halogenated marine steroid from an Okinawan sponge,Xestospongia sp., possessing potent antitumor activity

A novel chlorinated steroid, aragusterol C, was isolated from an Okinawan marine sponge of the genusXestospongia. The compound strongly inhibited the proliferation of KB cells in vitro, and also showed potent in vivo antitumor activity against L1210 cells in mice. The complete structure of aragusterol C was determined by spectroscopic analysis and X-ray crystallographic analysis.     

Effect of methotrexate on glycolysis of leukemia L 1210 cells cultivated in vitro]

Methotrexate, at non lethal doses, alters the glycolysis of leukaemic L 1210 cells. Glucose uptake and lactate excretion are increased but lactate/glucose ratio remains constant. The activity of glycolytic enzymes in the cytoplasm is increased and the level of intracellular ATP is greatly enhanced.     

Resolution of small G1 and G2 populations of L1210 leukemia by flow microfluorometric analysis aided by velocity sedimentation

Summary L1210 leukemic cells grown in vitro were subjected to kinetic analysis using a flow microfluorometer. A single broad peak was found for the DNA content distribution if unfractionated cells were used; prior fractionation using lg velocity sedimentation allowed the separation of small peaks with smaller (G₁) and larger (G₂) DNA contents from the dominant S phase peak with intermediate DNA content.This work was supported by grant number 5P01CA13053 awarded by the National Cancer Institute, DHEW USA, and by grant num ber RBI 76-1 from the Queen Wilhelmina Fund, The Netherlands.     

delta-9-Tetrahydrocannabinol (THC) inhibition of the membrane transport system for thymidine]

THC decreases 3H-thymidine uptake within 15 sec. after addition of the drug to the culture (L1210 murine lymphoma cells and human lymphocytes). Experiments performed at 0 degrees C indicate that THC has no action on thymidine binding to the carrier. THC in micromolar concentration inhibits DNA synthesis through a alteration of membrane configuration.     

Cytotoxic and antitumor activity of a new series of heterocyclic compounds: dipyrido (4,3-b) (3,4-f) indoles]

Among newly synthesized compounds derived from the dipyrido [4,3-b] [3,4-f] indole nucleus, two have proved to be particularly active in vitro and in vivo. Their cytotoxic effects on cultured cells have been determined. At non toxic doses, they displayed a pronounced inhibitory effect on experimental L1210 Leukemia. These compounds have a strong affinity for DNA molecules.     

Agglutination of leukemic cells and daunomycin entrapped erythrocytes with lectin in vitro and in vivo

Summary Wheat germ agglutinin (WGA) agglutinated the L₁₂₁₀ leukemic cells and daunomycin entrapped erythrocytes in vitro. Comparing with control preparations, the greatest increase in survival was obtained in vivo when the daunomycin entrapped erythrocytes and WGA were given to BDF₁ mice bearing L₁₂₁₀ cells.     

Oncostatic activity of extracts from Alangium vitiense on murine lymphoid neoplasms]

A total alkaloid and two purified alkaloid extracts of Alangium Vitiense were revealed by our experimental screening to be oncostatic on L1210 leukemia and two other lymphoid neoplasias in Mice. They are not active on myelomonocytoid leukemia WEHI3 nor on B16 melanoma.     

The antimitotic drug 4,6-dimethyl-2-amino-3,4,5-trimethoxyphenyl-pyrimidine inhibits the nucleoside transport system of cells from various animal species

4,6-dimethyl-2-amino-3,4,5-trimethoxyphenyl-pyrimidine (B-31) is a pyrimidine derivative previously reported to arrest the mitotic cycle of mammalian cells in metaphase. In the present study it is shown that B-31 also acts as a specific inhibitor of the cellular uptake of nucleosides. The uptake of purinic and pyrimidinic nucleosides is inhibited by 80–90% at concentrations in the range 5–20 μg/ml, whereas those of nucleobases, leucine, choline and glucose are unaltered at the maximum nontoxic dose of B-31 (25 μg/ml). Various mammalian (human, monkey and murine) and avian cell are equally sensitive to the inhibition of nucleoside transport. The antimitotic effect of B-31, by contrast, is species-specific: human cells are the most sensitive whereas monkey and chicken fibroblasts appear resistant to this effect. Both effects can be reversed by removal of B-31 from the medium; inhibition of nucleoside transport can also be reversed by high doses of the nucleosides themselves.     

Cytochemical study of leucocytes of DBA/2 Mice after leukemia L1210 tumor graft]

The growth of L 1210 leukemia in DBA/2 strain mouse, provokes in the grafted animals intraleucocytic enzymatic modifications. As increase of acid phosphatase and a decrease of beta-glucuronidase were observed in the lymphocytes, the level of polymorphonuclear non-specific esterase being decreased. The implications of these modifications in the host response toward the tumor is discussed.     

Antineoplastic activity of lipid-soluble dialkyl esters of methotrexate

Résumé L'action biologique de 6 esters liposolubles di-n-alkyle de la méthotrexate (MTX) a été comparée à celle du composé non estérifié. En tant qu'inhibiteurs de la réductase dihydrofolate de cellules leucémiques L1210 de la souris, les esters ont été moins efficaces que la MTX. In vivo, les esters dialkyles ont eu une action égale à celle de la MTX, en prolongeant la survie des souris inoculées par l'injection de cellules leucémiques L1210. Puisque les esters sont rapidement hydrolysés in vivo on conclut que l'action antitumeur chez la souris est due à la libération de la MTX.

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We thank Dr.Dorris J. Hutchison, Sloan-Kettering Institute for Cancer Research, for supplying mice bearing the L1210/A (XL) tumor; and Mr.C. J. Derr, Mr.J. C. Drake and Mr.S. T. Yancey for skilled technical assistance.     

Adenylate storage,metabolism and utilization in coelomic cells of the polychaeteNereis virens (Annelida,polychaeta)

Eleocytes are specialized coelomic cells in nereid annelids which assume a central role during germ cell development. They may contain extremely high concentrations of both adenosine monophosphate (AMP) and adenosine diphosphate (ADP) (each >10 mol/ml of cell vol.), whereas the adenosine triphosphate (ATP) content is comparatively low (0.8 mol/ml cell vol.).³¹P nuclear magnetic, resonance (NMR) studies of living eleocytes suggest the compartmentalization of both AMP and ADP in the large acidic vacuole characteristic for this cell type. Eleocytes are thus capable of storing high concentrations of ADP and AMP without inhibiting energy metabolism, by sequestering these compounds in a separate compartment. The high concentrations of both AMP and ADP in the eleocytes decrease in both males and females during the course of maturation. In eleocytes of male animals, the decline of the high nucleotide concentrations was accompanied by a transient increase of two intracellular nucleosides, inosine and guanosine. This suggests the degradation and further metabolism of nucleotides to the corresponding nucleosides. In culture, eleocytes release both inosine and guanosine into the medium. Both nucleosides are also present in the coelomic fluid, the common compartment for both eleocytes and germ cells. Both male and female germ cells incorporate¹⁴C-labelled inosine and guanosine in culture. For oocytes, the further incorporation of [¹⁴C]inosine into the RNA fraction could be demonstrated. The large adenylate pools in the eleocytes may be regarded as a store for purine compounds for later use by the growing germ cells to supplement nucleic acid synthesis. The supply of nucleic acid precursors seems to be another specific function of eleocytes related to gametogenesis, in addition to their known synthesis of vitellogenin.     

Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4

The African tree Combretum caffrum (Combretacae) has been found to contain a powerful inhibitor of tubulin polymerization (IC50 2-3 microM), the growth of murine lymphocytic leukemia (L 1210 and P 388 with ED50 approximately 0.003 microM and human colon cancer cell lines [(e.g. LoVo (ED50 = 0.005 microgram/ml), HT 29 (ED50 0.02 microgram/ml, Colo 205 (ED50 = 0.07 microgram/ml), DLD-1 (ED50 = 0.005 microgram/ml) and HCT-15 (ED50 = 0.0009 microgram/ml] designated combretastatin A-4 (1c). The structure assigned by spectral techniques was confirmed by synthesis.     

Primary antibody response in mice bearing leukemia L1210

Riassunto La risposta immunitaria primaria a globuli rossi di montone, studiata mediante la tecnica delle placche di Jerne in topi CDF₁ normali o portatori di leucemia L1210, indica che lo sviluppo neoplastico deprime la formazione di anticorpi umorali solo nel caso in cui l'antigene venga iniettato in fase avanzata della malattia.

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Supported in part by contract No. PH-43-68-1283 with Chemotherapy, National Cancer Institute, National Institutes of Health.     

The inhibitory effect of α-2-macroglobulin on tumour growth

Zusammenfassung Versuche an Leukämiezellen L 1210 und in vivo-Versuche an DÄNA 435-tragenden R-Ratten haben gezeigt, dass ₂-Makroglobulin selektiv das Tumorwachstum hemmt.     

Benützung der oszillographischen Polarographie in der Mikrobiologie

Summary Oscillographic polarography with alternating current was used for following the course of utilisation and metabolism of some amino acids, purine and pyrimidine bases, similarly as their nucleosides and nucleotides in the washed suspensions of resting cells and in growing cultures ofEscherichia coli. The Polaroscope P-524 was used with mercury dropping electrode. The method was described for the oscillopolarographic investigation of activity of some bacterial enzymes, as for example: asparaginase, some nucleodesaminases and enzymes involved in the cleavage of nucleosides.     

Die normale Zusammensetzung des Plasmaproteinfilmes an der Oberfläche von Kaninchenerythrocyten

Summary A plasma protein film is adsorbed at the surface of the red cells of rabbit. The percentage composition of this plasma protein film is different from the protein composition of plasma.-Globulin, lipoprotein and prealbumin are increased, albumin is decreased at the surface of the red cells.