phosphorus-radioisotopes and Leukemia--Lymphoid

Recent developments in recombinant DNA technology have made possible the production of gene probes consisting of cloned gene segments, cloned segments of DNA linked to genes, and synthetic gene fragments. Several methods have been developed by which these probes may be used for the diagnosis of human disease. This technology has been outstandingly successful for prenatal diagnosis and carrier detection in many genetic diseases. These methods have also been successfully applied to the analysis of human malignancies, by providing for the determination of cell lineage and clonality in lymphoid neoplasms. Finally, these methods have shown potential for rapid and sensitive diagnosis of some infectious diseases.

Topics: B-Lymphocytes; Bacterial Infections; Biotin; Cloning, Molecular; Deoxyribonucleotides; DNA; DNA Restriction Enzymes; DNA, Recombinant; Female; Genetic Carrier Screening; Genetic Diseases, Inborn; Genotype; Hemophilia A; Humans; Immunoglobulins; Infections; Leukemia, Lymphoid; Leukocytes; Male; Muscular Dystrophies; Nucleic Acid Hybridization; Phenylketonurias; Phosphorus Radioisotopes; Polymorphism, Genetic; Pregnancy; Prenatal Diagnosis; Receptors, Antigen, T-Cell; RNA; T-Lymphocytes; Virus Diseases

Topics: Animals; Bone Marrow; Bone Marrow Cells; Cell Survival; Dogs; Granulocytes; Half-Life; Hematopoiesis; Humans; In Vitro Techniques; Injections, Intramuscular; Injections, Intravenous; Isoflurophate; Kinetics; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Methods; Neutropenia; Neutrophils; Phosphorus Radioisotopes; Remission, Spontaneous; Time Factors

Topics: Anemia, Aplastic; Animals; Bacteriological Techniques; Bone Marrow; Glomerular Filtration Rate; Histological Techniques; Humans; Hypersplenism; Immunologic Techniques; Iodine Radioisotopes; Kidney; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Phosphorus Radioisotopes; Polycythemia Vera; Rabbits

Thirty-two patients with meningeal leukaemia who achieved meningeal remission with intrathecal methotrexate (MTX) plus dexamethasone (DMT) were entered in a randomized study of two maintenance treatments: (a) I6 patients received intermittent intrathecal doses of MTX plus DMT, and (b) I6 patients received intermittent intrathecal doses of radioactive chromic phosphate (CROP). The population and clinical characteristics of the cases assigned to each maintenance regimen were similar. The duration of meningeal remission was 55-600 + d (median 550 d) for the MTX and DMT group and 56-555 d (median 360 d) for the CROP group. There was no statistical difference (P greater than 0.05) between the curves of the two groups. Intrathecal CROP seems to be as effective as intrathecal MTX plus DMT as maintenance treatment for intrathecal MTX plus DMT induced meningeal remission. Further uses of this compound should be explored but it seems to be dangerous to administer it by lumbar puncture.

Topics: Adolescent; Adult; Child; Child, Preschool; Colloids; Dexamethasone; Female; Humans; Injections, Spinal; Leukemia, Lymphoid; Male; Meningitis; Methotrexate; Phosphorus Radioisotopes; Remission, Spontaneous; Time Factors

P-Glycoprotein (Pgp) is responsible for the energy-dependent efflux of many natural product oncolytics. Overexpression of Pgp may result in multidrug resistance (MDR). Modulators can block Pgp efflux and sensitize multidrug resistant cells to these oncolytics. To study the interaction of modulators with Pgp, Pgp-ATPase activity was examined, using plasma membranes isolated from the multidrug-resistant cell line CEM/VLB100. A survey of modulators indicated that verapamil, trifluoperazine, and nicardipine stimulated ATPase activity by 1.3- to 1.8-fold, whereas two others, trimethoxybenzoylyohimbine (TMBY) and vindoline, had no effect. Further evaluation showed that TMBY completely blocked the stimulation by verapamil of ATPase activity by competitive inhibition, with a Ki of 2.1 microM. When the effects of these two modulators on the formation of the enzyme-nucleotide complex important in the catalytic cycle were examined, verapamil increased the amount of vanadate-trapped 8-azido-[alpha-32P]ATP bound to Pgp by two-fold, whereas TMBY had no effect. Moreover, TMBY blocked the verapamil stimulation of vanadate-8-azido-[alpha-32P]ATP. Together, these data indicate that verapamil and TMBY bind to Pgp at a common site or overlapping sites, but only verapamil results in enhanced Pgp-ATP hydrolysis and formation of the vanadate-nucleotide-enzyme complex.

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Azides; Binding Sites; Calcium Channel Blockers; Cell Membrane; Drug Interactions; Drug Resistance, Multiple; Humans; Hydrolysis; Leukemia, Lymphoid; Phosphorus Radioisotopes; Protein Conformation; Stimulation, Chemical; Tumor Cells, Cultured; Vanadates; Verapamil; Vinblastine; Yohimbine

The effects of prolonged exposure to 2 and 10 microM 6-mercaptopurine (6MP) in the human lymphoblastic T-cell line MOLT-4 were studied with respect to cell-kinetic parameters, phosphoribosyl pyrophosphate (PRPP) and purine ribonucleotide levels, formation of 6MP-nucleotides, especially methyl-thio-IMP (Me-tIMP), DNA and RNA synthesis ([32P] incorporation), and [8-14C]6MP incorporation into newly synthesized DNA and RNA. The results provided new insights into the complex mechanism of action of 6MP in human malignant lymphoblasts. Exposure to 2 microM 6MP resulted in a rapid inhibition of purine de novo synthesis (PDNS) by increased levels of Me-tIMP, resulting in increased PRPP levels and decreased purine ribonucleotides, affecting cell growth and clonal growth, and less cell death. DNA synthesis decreased, associated with an increasing delay of cells in S phase. Incorporation of thioguanine nucleotides into newly synthesized DNA resulted in an increasing arrest of cells in G2 + M phase. RNA synthesis, initially decreased, recovered partially, associated with a recovery of purine ribonucleotides. New formation of 6MP-nucleotides (tIMP) was only detected within the first 24 hr, and 6MP levels in the culture medium were already undetectable after 6 hr of exposure to 2 microM, indicating a high rate of incorporation and complete conversion of 6MP within this period. Incorporation of 6MP-nucleotides into DNA was 5 times as high as incorporation into RNA. Exposure to 10 microM 6MP resulted in early cytotoxicity at 24 hr, associated with a complete inhibition of PDNS by a large pool of Me-tIMP and lower levels of purine ribonucleotides as compared to 2 microM 6MP. A more severe delay of cells in S phase was associated with an inhibition of DNA synthesis to 14% of control within the first 24 hr, and an arrest in G2 + M phase. Further increasing levels of Me-tIMP caused an arrest of cells and late cytotoxicity in S phase at 48 hr, preventing further progression into G2 + M phase. Our data suggest that inhibition of PDNS due to Me-tIMP is a crucial event in the mechanism of 6MP cytotoxicity. It is responsible for decreased RNA synthesis and decreased availability of natural deoxyribonucleotides, causing a delay of DNA synthesis in S phase. This enhances incorporation of 6MP as thioguanine nucleotides into DNA in the S phase and subsequent late cytotoxicity in the G2 phase. However, with high concentrations of 6MP, the large pool of Me-tIMP causes severe reduction o

Topics: Carbon Radioisotopes; Cell Cycle; DNA; Humans; Inosine Monophosphate; Leukemia, Lymphoid; Mercaptopurine; Phosphoribosyl Pyrophosphate; Phosphorus Radioisotopes; Ribonucleotides; RNA; Stem Cells; T-Lymphocytes; Thionucleotides

The human T lymphoblastoid cell line designated CCRF-CEM responds to phytohemagglutinin with a 3.7-fold enhancement of the 32PO4 incorporation into phosphatidylinositol. In myo-[2-3H]inositol-prelabeled CCRF-CEM cells, phytohemagglutinin induced a 3.3-fold accumulation of myo-[2-3H]inositol phosphate during 15 min incubation at 37 degrees C in the presence of 5 mM LiCl. Since Li+ is a potent inhibitor of myo-inositol-1-phosphatase, the results indicate that phytohemagglutinin induces the hydrolysis of inositol lipids in CCRF-CEM cells. In 32PO4-prelabeled CCRF-CEM cells, phytohemagglutinin induced a breakdown of 28% of [32P]phosphatidylinositol 4,5-bisphosphate 40-60 s after the stimulation. The decrease of [32P]phosphatidylinositol 4,5-bisphosphate was found as early as 10 s after the stimulation. This decrease was followed by an increased 32P-labeling of phosphatidic acid. In [2-3H]glycerol-prelabeled CCRF-CEM cells, phytohemagglutinin induced a transient accumulation of [3H]phosphatidic acid and [3H]diacylglycerol. The amount of [3H]phosphatidic acid in the stimulated cells was 3.7-times the control value at 2 min after the stimulation, whereas the amount of [3H]diacylglycerol in the stimulated cells was 1.5-times the control value at 5 min after the stimulation. In [3H8]arachidonate-prelabeled CCRF-CEM cells, phytohemagglutinin induced a transient accumulation of [3H]phosphatidic acid; the amount was 2.5-times the control value at 2 min after the stimulation. Quinacrine (1 mM) caused 41% reduction in the amount of [3H]phosphatidic acid accumulated by the stimulation in [2-3H]glycerol-prelabeled cells. Stimulation in a Ca2+-free saline containing 1 mM EGTA caused 53% reduction in the amount of [3H]phosphatidic acid accumulated by the stimulation. The results presented in this paper indicate that a human T lymphoblastoid cell line, CCRF-CEM, responds to phytohemagglutinin with a rapid turnover of inositol lipids.

Topics: Cell Line; Concanavalin A; Diglycerides; Glycerides; Humans; Kinetics; Leukemia, Lymphoid; Phosphatidic Acids; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Phospholipids; Phosphorus Radioisotopes; Phytohemagglutinins; T-Lymphocytes

Topics: Carbon Radioisotopes; Cell Line; Erythrocyte Membrane; Galactose; Glycophorins; Humans; Leukemia, Lymphoid; Methionine; Phosphates; Phosphorus Radioisotopes; Protein Biosynthesis; Protein Processing, Post-Translational; Radioisotope Dilution Technique; RNA, Messenger; Sialoglycoproteins; Sulfates; Sulfur Radioisotopes

Topics: Blood; Child; Extracorporeal Circulation; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus Radioisotopes; Spleen; Thymus Gland

Topics: Aged; Cyclophosphamide; Hodgkin Disease; Humans; Intestinal Absorption; Leukemia, Lymphoid; Leukemia, Myeloid; Middle Aged; Multiple Myeloma; Phosphates; Phosphorus Radioisotopes

Topics: Adolescent; Adult; Aged; Antibodies, Viral; Antigens, Viral; Biopsy; Burkitt Lymphoma; Cell Survival; Child; Child, Preschool; Chromatography, Gel; DNA, Viral; Female; Herpesvirus 4, Human; Hodgkin Disease; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Nucleic Acid Hybridization; Phosphorus Radioisotopes; Staining and Labeling

Topics: Acute Disease; Cell Nucleolus; Humans; Lectins; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Lymphocytes; Lymphoma, Non-Hodgkin; Phosphorus Radioisotopes; RNA, Neoplasm; RNA, Ribosomal

Activity of thymus adenylate cyclase was more than three times higher in leukemic AKR mice than in nonleukemic AKR mice and CBA mice. Preleukemic AKR mice that had no evidence of leukemia but were expected to soon develop the disease exhibited similarly elevated activities of thymus adenylate cyclase.

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Age Factors; Animals; Cyclic AMP; Enzyme Activation; Epinephrine; Leukemia, Lymphoid; Mice; Mice, Inbred AKR; Mice, Inbred CBA; Phosphorus Radioisotopes; Stimulation, Chemical; Thymus Gland

Topics: Adult; Aged; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Macrocytic; Bone Marrow; Cell Survival; Erythrocytes; Erythropoiesis; Female; Hematologic Diseases; Hemoglobins; Humans; Iron; Iron Radioisotopes; Isoflurophate; Leukemia, Lymphoid; Liver Cirrhosis; Male; Methods; Middle Aged; Phosphorus Radioisotopes; Polycythemia; Spherocytosis, Hereditary; Thalassemia

Topics: Aflatoxins; Animals; Cell Line; DNA; Dose-Response Relationship, Drug; Furans; HeLa Cells; Humans; Kinetics; Leukemia, Lymphoid; Mice; Mycotoxins; Nucleosides; Phosphorus Radioisotopes; RNA; Thymidine; Tritium; Uridine; Xanthenes

Topics: Base Sequence; Burkitt Lymphoma; Cell Line; Cells, Cultured; Centrifugation, Density Gradient; Chromatography, DEAE-Cellulose; Genes; Humans; Lectins; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphocyte Activation; Lymphocytes; Oligonucleotides; Pancreas; Phosphorus Radioisotopes; Purines; Remission, Spontaneous; Ribonucleases; RNA, Ribosomal

Topics: Aged; B-Lymphocytes; Chlorambucil; Chronic Disease; Female; Humans; Infections; Leukemia, Lymphoid; Male; Middle Aged; Phosphorus Radioisotopes; Prednisone; Prognosis

Topics: Adenosine Triphosphate; Base Sequence; Cell-Free System; Chromatin; DNA; DNA-Directed RNA Polymerases; DNA, Neoplasm; Escherichia coli; Female; Filtration; Hot Temperature; Humans; Leukemia, Lymphoid; Leukocytes; Nucleic Acid Hybridization; Phosphorus Radioisotopes; Placenta; Ribonucleases; RNA; Templates, Genetic; Transcription, Genetic; Tritium; Uracil Nucleotides

Topics: Burkitt Lymphoma; Cell Division; Cell Nucleus; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Humans; Lectins; Leukemia; Leukemia, Lymphoid; Leukocytes; Lymphocyte Activation; Lymphocytes; Molecular Weight; Peptide Hydrolases; Phosphoric Monoester Hydrolases; Phosphorus Radioisotopes; Proteins; Sodium Dodecyl Sulfate; Tritium

Topics: Agranulocytosis; Cell Division; DNA Replication; Humans; Kinetics; Leukemia, Lymphoid; Leukemia, Myeloid; Neutrophils; Phosphorus Radioisotopes

Topics: Burkitt Lymphoma; Cell Nucleus; Centrifugation, Density Gradient; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Phosphorus Radioisotopes; RNA, Neoplasm; Sucrose

Topics: Chromium Radioisotopes; Hodgkin Disease; Humans; Isotope Labeling; Leukemia, Lymphoid; Leukocyte Count; Leukocytes; Lung Neoplasms; Methods; Phosphorus Radioisotopes; Time Factors

Topics: Cell Nucleus; Centrifugation, Density Gradient; Humans; Leukemia, Lymphoid; Methods; Phosphates; Phosphorus Radioisotopes; RNA, Neoplasm

Topics: Chlorambucil; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Lymphocytes; Mechlorethamine; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes

Topics: Granulocytes; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Phosphorus; Phosphorus Radioisotopes

Topics: Chronic Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Humans; Leukemia; Leukemia, Lymphoid; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Skin

Topics: Leukemia; Leukemia, Lymphoid; Lymphatic Vessels; Phosphorus; Phosphorus Radioisotopes