mercaptopurine and purine

Topics: Antimetabolites, Antineoplastic; Bone Marrow; Child; Humans; Mercaptopurine; Methyltransferases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines

Topics: Azathioprine; Dactinomycin; Immune Tolerance; Immunity; Immunosuppressive Agents; Kidney Transplantation; Mercaptopurine; Purines; Radiation Effects; Research; Transplantation Immunology; Transplantation, Heterologous; Transplantation, Homologous; Twins

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Floxuridine; Fluorouracil; Folic Acid; Glutamine; Leukemia L1210; Mercaptopurine; Methotrexate; Mitomycin; Neoplasms; Neoplasms, Experimental; Pharmacology; Purines; Puromycin; Pyrimidines; Research; RNA; RNA, Neoplasm; Thioguanine; Thiouracil

Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity. The loss-of-fitness phenotype of NT5C2

Topics: 5'-Nucleotidase; Animals; Cell Proliferation; Clonal Evolution; Disease Models, Animal; Drug Resistance, Neoplasm; Female; Gain of Function Mutation; Guanosine; HEK293 Cells; Humans; IMP Dehydrogenase; Male; Mercaptopurine; Mice; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines; Receptor, Notch1; Recurrence; Xenograft Model Antitumor Assays

Relapse is the leading cause of mortality in children with acute lymphoblastic leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in ALL combination therapy. Using whole-exome sequencing, we identified relapse-specific mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encodes a rate-limiting purine biosynthesis enzyme, in 24/358 (6.7%) relapsed childhood B cell ALL (B-ALL) cases. All individuals who harbored PRPS1 mutations relapsed early during treatment, and mutated ALL clones expanded exponentially before clinical relapse. Our functional analyses of PRPS1 mutants uncovered a new chemotherapy-resistance mechanism involving reduced feedback inhibition of de novo purine biosynthesis and competitive inhibition of thiopurine activation. Notably, the de novo purine synthesis inhibitor lometrexol effectively abrogated PRPS1 mutant-driven drug resistance. These results highlight the importance of constitutive activation of the de novo purine synthesis pathway in thiopurine resistance, and they offer therapeutic strategies for the treatment of relapsed and thiopurine-resistant ALL.

Topics: Adolescent; Child; Child, Preschool; Exome; Feedback, Physiological; Female; High-Throughput Nucleotide Sequencing; Humans; Infant; Leukemia, B-Cell; Male; Mercaptopurine; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines; Recurrence; Ribose-Phosphate Pyrophosphokinase; Tetrahydrofolates

Topics: Anti-Inflammatory Agents; Azathioprine; Female; Fetus; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Mercaptopurine; Pregnancy; Pregnancy Complications; Purines; Remission Induction; Risk Assessment; Risk Factors; Treatment Outcome

The thiopurines, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), are used in the treatment of leukemia. Incorporation of deoxythioguanosine nucleotides (dG(s)) into the DNA of thiopurine-treated cells causes cell death, but there is also evidence that thiopurine metabolites, particularly the 6-MP metabolite methylthioinosine monophosphate (MeTIMP), inhibit de novo purine synthesis (DNPS). The toxicity of DNPS inhibitors is influenced by methylthioadenosine phosphorylase (MTAP), a gene frequently deleted in cancers. Because the growth of MTAP-deleted tumor cells is dependent on DNPS or hypoxanthine salvage, we would predict such cells to show differential sensitivity to 6-MP and 6-TG. To test this hypothesis, sensitivity to 6-MP and 6-TG was compared in relation to MTAP status using cytotoxicity assays in two MTAP-deficient cell lines transfected to express MTAP: the T-cell acute lymphoblastic leukemic cell line, Jurkat, transfected with MTAP cDNA under the control of a tetracycline-inducible promoter, and a lung cancer cell line (A549-MTAP(-)) transfected to express MTAP constitutively (A549-MTAP(+)). Sensitivity to 6-MP or methyl mercaptopurine riboside, which is converted intracellularly to MeTIMP, was markedly higher in both cell lines under MTAP(-) conditions. Measurement of thiopurine metabolites support the hypothesis that DNPS inhibition is a major cause of cell death with 6-MP, whereas dG(s) incorporation is the main cause of cytotoxicity with 6-TG. These data suggest that thiopurines, particularly 6-MP, may be more effective in patients with deleted MTAP.

Topics: Antimetabolites, Antineoplastic; Cell Line, Tumor; Drug Resistance, Neoplasm; Gene Deletion; Humans; Immunoblotting; Mercaptopurine; Neoplasms; Purine-Nucleoside Phosphorylase; Purines; Thioguanine; Thioinosine; Thionucleotides

To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT).. We studied these metabolites in 229 blood samples from 18 children with ALL (N = 16) or NHL (N = 2) on 6MP/Methotrexate maintenance therapy.. DNA-6TGN levels were significantly correlated to E-6TGN (r (p) = 0.66, p = 0.003) with a trend to reach a plateau at high E-6TGN levels. To explore the relative DNA incorporation of 6TGN in relation to cytosol 6TGN levels, a DNA-6TGN index was calculated as DNA-6TGN/E-6TGN. The DNA-6TGN index was inversely correlated to E-6TGN (r (p) = -0.58, p = 0.012), which implies that with increasing levels of E-6TGN relatively less 6TGN are incorporated into DNA. E-MeMP levels were correlated to the DNA-TGN index (r (p) = 0.60, p = 0.008), indicating that high levels of MeMP result in enhanced DNA-6TGN incorporation, possibly due to inhibition of purine de novo synthesis, mediated by some of the methylated 6MP metabolites.. DNA-6TGN may prove to be a more relevant pharmacokinetic parameter for monitoring 6MP treatment intensity than the previously used erythrocyte 6MP metabolites levels. Prospective clinical trials are needed to evaluate the usefulness of DNA-6TGN for individual dose adjustments.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytosol; DNA; Drug Monitoring; Erythrocytes; Female; Guanine Nucleotides; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines; Thionucleotides

A survey is given of our present investigations of the pharmacokinetics of 6MP and the effects of the combination of MTX and 6MP on purine and pyrimidine metabolism. Both drugs are used in the oral maintenance therapy of ALL in children. The very low serum-concentrations after oral administration of 6MP and the short serum-half-life-times after intravenous administration point to more efficacy after prolonged intravenous infusion. The penetration of 6MP in the cerebrospinal fluid after intravenous administration could account for (prophylactic) treatment of the CNS in ALL. Pretreatment of leukemic lymphoblasts with MTX results in an increase of intracellular PRPP due to inhibition of purine de novo synthesis. This can be used for an increased incorporation and conversion of 6MP. Thus, increased incorporation and conversion of 6MP can be obtained when 6MP is added to MTX-pretreated leukemic lymphoblasts at that point of time where MTX causes maximal PRPP accumulation. This will result in increased incorporation of 6MP into nucleic acids and thus in enhanced cytotoxicity. Pharmacokinetic and metabolic investigations of 6MP and MTX could lead to a more rational and more effective use of both agents in patients with ALL.

Topics: Animals; Child; Dogs; Half-Life; Humans; Infusions, Parenteral; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Methotrexate; Purines; Pyrimidines

Topics: Adenine; Animals; Antimetabolites; Guanine; Mercaptopurine; Metabolism; Mice; Neoplasms; Neoplasms, Experimental; Nucleosides; Purine Nucleosides; Purines; Research

1. The formation of adenosine 5'-phosphate, guanosine 5'-phosphate and inosine 5'-phosphate from [8-(14)C]adenine, [8-(14)C]guanine and [8-(14)C]hypoxanthine respectively in the presence of 5-phosphoribosyl pyrophosphate and an extract from Ehrlich ascites-tumour cells was assayed by a method involving liquid-scintillation counting of the radioactive nucleotides on diethylaminoethylcellulose paper. The results obtained with guanine were confirmed by a spectrophotometric assay which was also used to assay the conversion of 6-mercaptopurine and 5-phosphoribosyl pyrophosphate into 6-thioinosine 5'-phosphate in the presence of 6-mercaptopurine phosphoribosyltransferase from these cells. 2. At pH 7.8 and 25 degrees the Michaelis constants for adenine, guanine and hypoxanthine were 0.9 mum, 2.9 mum and 11.0 mum in the assay with radioactive purines; the Michaelis constant for guanine in the spectrophotometric assay was 2.6 mum. At pH 7.9 the Michaelis constant for 6-mercaptopurine was 10.9 mum. 3. 25 mum-6-Mercaptopurine did not inhibit adenine phosphoribosyltransferase. 6-Mercaptopurine is a competitive inhibitor of guanine phosphoribosyltransferase (K(i) 4.7 mum) and hypoxanthine phosphoribosyltransferase (K(i) 8.3 mum). Hypoxanthine is a competitive inhibitor of guanine phosphoribosyltransferase (K(i) 3.4 mum). 4. Differences in kinetic parameters and in the distribution of phosphoribosyltransferase activities after electrophoresis in starch gel indicate that different enzymes are involved in the conversion of adenine, guanine and hypoxanthine into their nucleotides. 5. From the low values of K(i) for 6-mercaptopurine, and from published evidence that ascites-tumour cells require supplies of purines from the host tissues, it is likely that inhibition of hypoxanthine and guanine phosphoribosyltransferases by free 6-mercaptopurine is involved in the biological activity of this drug.

Topics: Adenine; Adenine Nucleotides; Adenosine Monophosphate; Animals; Ascites; Carcinoma, Ehrlich Tumor; Diphosphates; Electrophoresis; Enzyme Inhibitors; Glucosyltransferases; Guanine; Guanine Nucleotides; Hypoxanthines; Kinetics; Mercaptopurine; Nucleotides; Pharmacology; Purines; Research; Spectrophotometry; Transferases; Xanthines

Topics: Adenine; Animals; Antimetabolites; Antineoplastic Agents; Azaserine; Carcinoma, Squamous Cell; Glycine; Hypoxanthines; Imidazoles; Leukemia L1210; Mercaptopurine; Nucleotides; Pharmacology; Purines; Research; Ribonucleotides; Thioguanine; Tissue Culture Techniques; Xanthines

Topics: Adenine; Adenine Nucleotides; Carbon Isotopes; Chromatography; Culture Media; Guanine; Guanine Nucleotides; Histidine; Mercaptopurine; Metabolism; Nucleosides; Purines; Research; Ribonucleosides; Salmonella typhimurium; Spectrophotometry

Topics: Animals; Antimetabolites; Caffeine; Carcinoma; Carcinoma, Ehrlich Tumor; Liver; Mercaptopurine; Metabolism; Mice; Purines; Pyrimidines; Research; Sulfhydryl Compounds; Theobromine; Theophylline

Topics: Aminopterin; Animals; Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Geriatrics; Histological Techniques; Hydrocortisone; Leukemia; Leukemia, Lymphoid; Leukocytosis; Mercaptopurine; Methotrexate; Mice; Polycythemia Vera; Purines; Research; Tissue Culture Techniques

Topics: Animals; Antineoplastic Agents; Aspartic Acid; Azaguanine; Carbon Isotopes; Glycine; Guanine Nucleotides; Imidazoles; Liver; Lyases; Mercaptopurine; Metabolism; Mice; Neoplasms, Experimental; Nucleotides; Pharmacology; Purines; Research; Sarcoma 180; Thioguanine

Topics: Bone Marrow; Injections, Intravenous; Leukopenia; Mercaptopurine; Mice; Neoplasms; Nucleosides; Pharmacology; Purines; Pyrimidines; Research; Thioinosine; Thrombocytopenia; Toxicology

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: Alkylating Agents; Animals; Antibody Formation; Antineoplastic Agents; Azaserine; Imidazoles; Mercaptopurine; Mice; Pharmacology; Purines; Rats; Research; Sarcoma 180; Tetanus Toxoid; Thioguanine; Toxicology

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carbonates; Chemistry, Pharmaceutical; Leukemia L1210; Mercaptopurine; Mice; Purines; Research; Sarcoma 180; Tissue Culture Techniques

Topics: Adenine Nucleotides; Antimetabolites; Antineoplastic Agents; Azaguanine; Chromatography; Diphosphates; Enzyme Inhibitors; Glutamine; Mercaptopurine; Nucleotides; Purines; Pyrazoles; Pyrimidines; Research; Thioguanine; Transferases; Ultraviolet Rays

Topics: Abnormalities, Drug-Induced; Adenine; Female; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Pharmacology; Placenta; Pregnancy; Purines; Pyrazoles; Pyrimidines; Rats; Research; Teratogenesis; Thioguanine; Toxicology

Topics: Adenine; Amino Acids; Animals; Antimetabolites; Antineoplastic Agents; Azaserine; Carbon Isotopes; Glycine; Guanine; Mercaptopurine; Metabolism; Mice; Neoplasm Transplantation; Nucleotides; Pharmacology; Purines; Research; Sarcoma 180

Topics: Adenine; Antineoplastic Agents; Drug Therapy; Fever; Hematocrit; Leukemia; Leukocyte Count; Mercaptopurine; Purines; Thioguanine; Toxicology

Topics: 2-Aminopurine; Adenine; Adenine Nucleotides; Azaguanine; Bacillus subtilis; Guanine; Guanine Nucleotides; Hypoxanthines; Mercaptopurine; Metabolism; Mutation; Nucleosides; Nucleotides; Pharmacology; Purines; Research; Xanthines

Topics: Antibody Formation; Antimetabolites; Antineoplastic Agents; Carbon Isotopes; Cell Nucleus; Cytosine; Guanine; Leucine; Leukocytes; Lysine; Mercaptopurine; Metabolism; Orotic Acid; Pharmacology; Proteins; Purines; Research; RNA; Thioguanine; Uracil; Uric Acid; Xanthines

Topics: Antineoplastic Agents; Drug Therapy; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Prognosis; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Allografts; Animals; Antineoplastic Agents; Cyclophosphamide; Dactinomycin; Dogs; Humans; Imidazoles; Kidney Transplantation; Mechlorethamine; Mercaptopurine; Purines; Radiation Effects; Transplantation, Homologous

Topics: Adenine; Caffeine; Carbon Isotopes; Guanine; Intestine, Small; Intestines; Mercaptopurine; Pharmacology; Physiology; Purines; Pyrimidines; Rats; Research; Theobromine; Theophylline; Uracil; Uric Acid; Xanthines

Topics: Antimetabolites; Gout; Humans; Leukemia; Mercaptopurine; Pharmacology; Psoriasis; Purines; Pyrazoles; Pyrimidines

Topics: Animals; Antineoplastic Agents; Mercaptopurine; Metabolism; Mice; Purines; Sulfhydryl Compounds; Sulfur Isotopes; Urine

Topics: Animals; Biosynthetic Pathways; Carbon Isotopes; Carcinoma; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Formates; Glycine; Leukemia L1210; Mercaptopurine; Metabolism; Nucleotides; Purines; Research; RNA; RNA, Neoplasm; Sarcoma 180

Topics: Animals; Chemical Phenomena; Chemistry; Mammals; Mercaptopurine; Oxidation-Reduction; Oxidoreductases; Purines; Research; Xanthine Oxidase

Topics: Animals; Feces; Mercaptopurine; Metabolism; Mice; Purines; Research; Sarcoma 180; Sulfur Isotopes; Urine

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; DNA; DNA, Neoplasm; Fluorouracil; Idoxuridine; Liver Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Nucleosides; Nucleotides; Purines; Research; RNA; RNA, Neoplasm; Sarcoma 180; Thioguanine; Uracil Mustard

Topics: Acridines; Antineoplastic Agents; Arsenicals; Azaguanine; Azaserine; Busulfan; Cell Division; Chloramines; Colchicine; Humans; Mercaptopurine; Pharmacology; Purines; Thiotepa; Triethylenemelamine

Topics: Cryptophyta; Eukaryota; Humans; Mercaptopurine; Paramecium; Purines

Topics: Mercaptopurine; Oxidoreductases; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Animals; Cyclophosphamide; Dactinomycin; Dogs; Kidney; Kidney Transplantation; Mercaptopurine; Nitrogen Mustard Compounds; Purines; Radiation Effects

Coultas, M. Katharine (Sloan-Kettering Institute for Cancer Research, Rye, N.Y.) and Dorris J. Hutchison. Metabolism of resistant mutants of Streptococcus faecalis. IV. Use of a biophotometer in growth-curve studies. J. Bacteriol. 84:393-401. 1962. - Analysis of data obtained using the Bonet-Maury and Jouan biophotometer has shown it to be an accurate, automatic device for recording an entire bacterial growth curve, from which quantitative measurements of growth rate can be calculated. Growth rate values obtained in this manner agree with those obtained by conventional methods. The instrument is described in detail and reference is given to other uses of this type of photometer. The growth curves of Streptococcus faecalis ATCC 8043 and three mutants resistant to purine analogues were compared in media with and without a purine. Differences in these growth curves were evident. In the purine-deficient medium SF/AZAG, the 8-azaguanine-resistant mutant had the shortest doubling time, 61 min, followed by the two 6-mercaptopurine-resistant mutants (SF/MPcc, 72 min; SF/MP, 91 min), and finally the wild strain with a doubling time of 135 min. In the medium supplemented with xanthine, the respective doubling times were 52, 61, 68, and 68 min.

Topics: Azaguanine; Drug Resistance, Microbial; Enterococcus faecalis; Mercaptopurine; Photometry; Purines

Topics: Adenocarcinoma; Antimetabolites; Antineoplastic Agents; Chemical Phenomena; Chemistry; Mercaptopurine; Pharmacology; Purines; Research; Sulfhydryl Compounds; Thioguanine

Topics: Carcinoma; Carcinoma, Squamous Cell; Humans; Mercaptopurine; Purines

Topics: Animals; Antineoplastic Agents; Ascites; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Purines; Sulfhydryl Compounds

Topics: Humans; Imidazoles; Mercaptopurine; Purines

Topics: Antimetabolites; Azaguanine; Butylene Glycols; Enzymes; Ethionine; Meprobamate; Mercaptopurine; Pentobarbital; Phenobarbital; Purines; Radiation Effects; Tranquilizing Agents

Topics: Antimetabolites; Child; Humans; Infant; Leukemia; Mercaptopurine; Purines; Thioinosine

Topics: Animals; Antineoplastic Agents; Azaguanine; Mercaptopurine; Purines; Rats

Topics: Mercaptopurine; Purines

Topics: Mercaptopurine; Purines

Topics: Animals; Mercaptopurine; Mice; Purines; Ribonucleosides; Selenium

Topics: Drug Tolerance; Immune Tolerance; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Animals; Leukemia; Leukemia, Experimental; Mercaptopurine; Purines

Topics: Animals; Enzymes; Humans; Mercaptopurine; Purines; Research; Tissue Culture Techniques

Topics: Acute Disease; Child; Humans; Infant; Leukemia; Mercaptopurine; Prednisone; Purines

Topics: Mercaptopurine; Metabolic Networks and Pathways; Purines; Uric Acid

Topics: Mercaptopurine; Purines; Structure-Activity Relationship

Topics: Antimetabolites; Colorimetry; Mercaptopurine; Purines

Topics: Animals; Azaguanine; Guanine; Mercaptopurine; Metabolic Networks and Pathways; Purines; Rats

Topics: In Vitro Techniques; Mercaptopurine; Metabolic Networks and Pathways; Nucleic Acids; Purines; Thioguanine

Topics: Cortisone; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Mercaptopurine; Purines

Topics: Animals; Anti-Bacterial Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Mercaptopurine; Neoplasms; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines

Topics: Acute Disease; Adrenocorticotropic Hormone; Cortisone; Leukemia; Mercaptopurine; Purines

Topics: Cortisone; Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Mononuclear Phagocyte System; Neoplasms; Purines

Topics: Animals; Liver; Mercaptopurine; Nucleic Acids; Purines; Rats

Topics: 2-Aminopurine; Azaguanine; Cell Division; Mercaptopurine; Plants; Purines

Topics: Animals; Folic Acid Antagonists; Leukemia, Experimental; Mercaptopurine; Methotrexate; Mice; Purines

Topics: Humans; Mercaptopurine; Nucleic Acids; Purines

Topics: Animals; Leukemia; Leukemia, Experimental; Mercaptopurine; Phosphorus; Purines; Rats; Thiotepa

Topics: Animals; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Mercaptopurine; Purines

Topics: Antineoplastic Agents; Leukemia; Mercaptopurine; Purines

Topics: Aminopterin; Child; Cortisone; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Purines

Topics: Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Abnormalities, Severe Teratoid; Mercaptopurine; Purines

Topics: Humans; Leukemia; Mercaptopurine; Purines

Topics: Arylsulfonates; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

The partial mitotic inhibition caused by 6-mercaptopurine in tissue cultures of Crocker mouse sarcoma 180 and embryonic mouse skin is blocked by co-enzyme A. 6-Mercaptopurine and coenzyme A also have opposite effects on mitochondrial morphology. Mitochondria in cells treated with 6-mercaptopurine become thin and fragmented. Coenzyme A blocks this effect, and alone coenzyme A makes for longer and thicker mitochondria. 6-Mercaptopurine inhibits lipogenesis in embryo skin fibroblasts, and this inhibition is partly counteracted by coenzyme A, which by itself makes for a greater accumulation of lipid droplets in the cytoplasm. It is suggested that at least one part of the action by which 6-mercaptopurine decreases mitotic incidence in tissue cultures may be an interference on the part of 6-mercaptopurine, acting as an antimetabolite of coenzyme A, in mitochondrial function related to cell division.

Topics: Animals; Antimetabolites; Cell Division; Coenzyme A; Coenzymes; Cytoplasm; Fibroblasts; Mercaptopurine; Mice; Mitochondria; Mitosis; Purines; Sarcoma 180; Tissue Culture Techniques

Topics: Acute Disease; Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Animals; Leukemia; Leukemia, Experimental; Mercaptopurine; Mitosis; Neoplasms, Experimental; Phosphoramides; Poisons; Purines; Triethylenemelamine; Triethylenephosphoramide

Topics: Animals; Mercaptopurine; Neoplasms, Experimental; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Mercaptopurine; Metabolism; Purines

Topics: Animals; Mercaptopurine; Mice; Nucleotides; Purines

Topics: Child; Hematopoiesis; Hodgkin Disease; Humans; Mercaptopurine; Purines

Topics: Humans; Lactobacillus; Mercaptopurine; Purines

Topics: Animals; Mercaptopurine; Purines; Rana pipiens; Wound Healing

Topics: Enterococcus faecalis; Humans; Mercaptopurine; Purines; Streptococcus

Topics: Animals; Fetus; Mercaptopurine; Purines; Rats; Reproduction

Topics: Animals; Mercaptopurine; Neoplasms, Experimental; Purines; Sarcoma, Experimental; Tissue Culture Techniques

Topics: Humans; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Purines

Topics: Acute Disease; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines

Topics: Animals; Leukemia, Experimental; Mercaptopurine; Mice; Purines

Topics: Animals; Mercaptopurine; Neoplasms, Experimental; Purines

Topics: Animals; Azaguanine; Brain; Brain Neoplasms; Glycols; Guanine; Mercaptopurine; Neoplasms, Experimental; Purines

Topics: Humans; Mercaptopurine; Purines

Topics: Humans; Mercaptopurine; Purines

Topics: Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Mercaptopurine; Neoplasms; Purines

Topics: Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Mercaptopurine; Neoplasms; Purines

Topics: Arylsulfonates; Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Humans; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Biomedical Research; Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Antimetabolites; Leukemia; Mercaptopurine; Purines

Topics: Animals; Mercaptopurine; Mice; Purines; Sarcoma 180; Sarcoma, Experimental

Topics: Lacticaseibacillus casei; Lactobacillus; Mercaptopurine; Metabolic Networks and Pathways; Purines

Topics: Antimetabolites; Leukemia; Mercaptopurine; Purines

Topics: Busulfan; Cortisone; Cysteamine; Ethylamines; Leukemia; Mercaptopurine; Phosphoramides; Phosphorus; Phosphorus, Dietary; Purines; Triethylenephosphoramide

Topics: Adenine; Animals; Humans; Leukemia, Experimental; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines