azaguanine and Leukemia

Topics: Aminopterin; Antineoplastic Agents; Asparaginase; Azaguanine; Brain Neoplasms; Cyclophosphamide; Cytarabine; Encephalitis; Folic Acid Antagonists; Gold Radioisotopes; Humans; Injections, Spinal; Kinetics; Leukemia; Lumbar Vertebrae; Methotrexate; Thiotepa; Vinca Alkaloids

The involvement of apoptosis in the cytotoxicity mediated by nucleoside analogues, namely azaguanine, and its implication in resistance are not well understood. Using human T-cell acute lymphoblastic leukemia cell lines, sensitive (CEM cells) and resistant to azaguanine (CM3 cells), we observe a decrease in the expression of proapoptotic proteins in CM3 cells, which may be related to the resistance to cell death induced by azaguanine. On the other hand, CM3 cells lack cross resistance with other anticarcinogenic drugs, suggesting that azaguanine may be used alternatively in the presence of chemoresistance. A better knowledge of the apoptotic pathways involved in leukemic cell death resistance may contribute to the development of therapeutic strategies, aimed to prevent chemotherapy resistance.

Topics: Antimetabolites, Antineoplastic; Apoptosis; Azaguanine; Cell Line, Tumor; Drug Resistance, Neoplasm; Humans; Immunophenotyping; Leukemia

A simple and convenient method for efficiently establishing 8-azaguanine-resistant mutant leukemia and myeloma cell lines (for example, the T cell lines Jurkat and CCRF-CEM, human myeloid/macrophage-like cell lines HL60 and U937, Burkitt lymphoma line Raji and the human myeloma line RPMI 8226), is described. The method relies on culturing the cell lines in RPMI 1640 medium containing 8-azaguanine and supplemented with 15% heat-inactivated fetal calf serum and large amounts of amino acids and vitamins, and removes the necessity for pretreatment with mutagenic reagents such as ethyl methylsulfonate or X-irradiation. The possibility of obtaining mutant cell lines using the method described here is about 15 times greater than using media without high levels of amino acids and vitamins. Hybridomas produced between mitogen-activated human peripheral blood lymphocytes and an 8-azaguanine-resistant Jurkat mutant cell line (established by this method) were shown to produce soluble T cell-derived macrophage activating factor (MAF)-like material.

Topics: Antigens, Surface; Azaguanine; Cell Line; Culture Media; DNA; Drug Resistance; Humans; Hybridomas; Hypoxanthine; Hypoxanthines; Leukemia; Lymphokines; Macrophage-Activating Factors; Plasmacytoma; T-Lymphocytes; Thioguanine

Topics: 2-Aminopurine; Aminopterin; Animals; Aspartic Acid; Azaguanine; Biological Products; Colchicine; Cortisone; Glutamates; Leukemia; Leukemia L1210; Leukemia, Experimental; Mercaptopurine; Methotrexate; Mice; Pharmacology; Purines; Research; Tryptophan; Vinblastine

Topics: Aminopterin; Antineoplastic Agents; Azaguanine; Carbohydrate Metabolism; In Vitro Techniques; Lactates; Leukemia; Leukocytes; Mechlorethamine; Mercaptopurine; Metabolism; Neoplasms; Prednisone; Research; Thiotepa; Vinblastine

Topics: Animals; Antineoplastic Agents; Azaguanine; Leukemia; Leukemia L1210; Nucleic Acids; Protein Biosynthesis; Proteins; Purines

Topics: Animals; Antineoplastic Agents; Azaguanine; Fluorouracil; Leukemia; Leukemia, Lymphoid; Lymphoma; Methotrexate; Mice; Nucleotides; Pyrimidines

Topics: Animals; Azaguanine; DNA; DNA, Neoplasm; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Neoplasms

Topics: Animals; Azaguanine; Leukemia; Leukemia P388; Leukemia, Experimental; Nucleotidyltransferases; Purines; Pyrophosphatases; Transferases

Topics: Animals; Antineoplastic Agents; Azaguanine; Leukemia; Leukemia, Experimental

Topics: Azaguanine; Guanine; Leukemia