Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sublines with single or multiple defects in purine "salvage" enzymes were isolated from the Chinese hamster fibroblastic line GMA32 through single or successive one-step selections for resistance to purine analogs. They were examined for their ability to incorporate purine bases and nucleosides into macromolecules, for their sensitivity to growth inhibitory purines, and for their rescue by exogenous purines from deprivation imposed by metabolic inhibitors of endogenous synthesis. The results show that a deficiency of either adenosine kinase (EC 2.7.1.20), adenine phosphoribosyltransferase (EC 2.4.2.7) or hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) abolishes the ability of adenine to cause cell death by interfering with pyrimidine synthesis; on the other hand, the pyrimidine starvation caused by adenosine is fully prevented only by a deficiency of adenosine kinase.
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PMID:The control of cell proliferation by preformed purines: a genetic study. I. Isolation and preliminary characterization of Chinese hamster lines with single or multiple defects in purine "salvage" pathways. 19 54

Concentration dependence of mutation in equigenerational exposures to methyl, ethyl, propyl, and butyl methanesulfonates has been determined in diploid human lymphoblasts and Salmonella typhimurium. Forward mutation was measured at the hypoxanthine guanine phosphoribosyltransferase locus in human lymphoblasts and at the putative guanine phosphoribosyltransferase locus in S. typhimurium. Reverse mutation at the his G46 locus was also measured in S. typhimurium. This analysis and previous reports support the conclusion that S. typhimurium and mammalian cells are essentially equisensitive to the mutagenic effects of ethyl methanesulfonate when concentration and exposure time are taken into account. Comparison of forward and reverse mutation assays in S. typhimurium reveals no important differences in sensitivities for the four compounds studied.
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PMID:Alkyl methane sulfonate mutation of diploid human lymphoblasts and Salmonella typhimurium. 20 53

Exogenous guanine was found to be incorporated into the nucleic acids of Chlamydia psittaci when the parasite was grown in HeLa cells containing hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) activity but not when the parasite was grown in transferase-deficient HeLa cells. No evidence for a chlamydia-specific transferase activity was found in either transferase-containing or transferase-deficient infected HeLa cells. It is concluded that C. psittaci is incapable of metabolizing guanine, but that the parasite can use host-generated guanine nucleotides as precursors for nucleic acid synthesis.
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PMID:Use of HeLa cell guanine nucleotides by Chlamydia psittaci. 47 49

Rabbit antisera have been produced against each of three purified human enzymes: a cytoplasmic form of NADP-linked isocitrate dehydrogenase (IDH, EC 1.1.1.42), phosphoglucose isomerase (PGI, EC 5.3.1.9), and hypoxanthine guanine phosphoribosyltransferase (HGPRT, EC 2.4.2.8), and they have been used for immunoprecipitation reactions to detect human-specific enzymes in various human-mouse somatic cell hybrids. Under optimal conditions, enzyme activity was eliminated from human cell lysate, but no reduction of enzyme activity was found in the mouse cell lysate. Differential enzyme precipitation by these human-specific antisera was observed in human-mouse hybrid cells. Analysis on starch gel electrophoresis revealed that not only the human homodimer, but also human-mouse heterodimer molecules, in cases of PGI and IDH, were precipitated. Thus this method is sensitive and allows quantitative determination of human-specific enzymes. The presence of a human-specific enzyme identified by this method correlated with the presence of a particular human chromosome permitting assignments of the human cytoplasmic forms of NADP-linked IDH, human PGI, and human HGPRT genes to chromosomes 2, 19, and X, respectively. These assignments are consistent with published data (Ruddle, 1973).
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PMID:Immunochemical detection of human enzymes in hybrid cells. 98 36

Analysis of human-Chinese hamster somatic cell hybrids with spontaneously derived chromosome structural changes has provided data for the regional and subregional localization of gene loci which have previously been assigned to human chromosomes 2, 12, and X. Correlation of the expression of human gene loci with the human chromosome complements present in somatic cell hybrids indicates that the cytoplasmic malate dehydrogenase (MDH1) locus is in the 2p23yields2pter region, and red cell acid phosphatase (AcP1) is at or adjacent to 2p23. The cytoplasmic isocitrate dehydrogenase (IDH1) locus is at or adjacent to 2q11, peptidase B (Pep B) is at or adjacent to 12q21, lactate dehydrogenase B (LDH B) is in the 12q21yiedls12pter region, glucose-6-phosphate dehydrogenase (G6PD) is in the Xq24yieldsXqter region, and the gene loci for phosphoglycerate kinase (PGK), alpha-galactosidase (alpha-gal), and hypoxanthine guanine phosphoribosyltransferase (GPRT) are in the Xp21yieldsXq24 region.
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PMID:Localization of human gene loci using spontaneous chromosome rearrangements in human-Chinese hamster somatic cell hybrids. 117 70

A spectrophotometric method for the determination of 5-phosphoribosyl 1-pyrophosphate (PRPP) is presented which shows several advantages in comparison to the radiochemical techniques, such as a relatively simple, rapid and less expensive procedure. This technique has been used to evaluate PRPP content in erythrocytes, leukocytes and lymphocytes of normal subjects and individuals with partial hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) deficiency. The results obtained proved to be completely reliable in both groups of subjects examined, with values of PRPP similar to those observed by radiochemical techniques.
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PMID:An improved method for the determination of 5-phosphoribosyl 1-pyrophosphate. 118 52

A genetic assay is described in which a mouse/human hybrid cell line R3-5 containing a single human chromosome (a monochromosomal hybrid) is used to detect chemically induced aneuploidy. In this assay the frequency of chromosome loss determined by the cloning efficiency of the cells in a selection medium is used as an index for the potential of a chemical to induce aneuploidy. The hybrid cells are deficient in hypoxanthine guanine phosphoribosyltransferase (HGPRT) and contain human chromosome 2, marked with Ecogpt, an E. coli gene for xanthine guanine phosphoribosyltransferase. These cells with a genotype of hgprt-/Ecogpt+ can grow in medium containing mycophenolic acid and xanthine (MX medium) but not in medium containing 6-thioguanine (6-TG). The loss of the human chromosome from R3-5 cells as a result of chemical treatment produces cells with a genotype of hgprt-/Ecogpt- which are capable of growth in the medium containing 6-TG. Thus, the cloning efficiency of cells treated with a test chemical in 6-TG provides a method to determine the frequency of cells that have lost the human chromosome. Two chemicals, colcemid and nocodazole, previously known to induce aneuploidy in mammalian cells were used for a preliminary evaluation of this test system. Both of these compounds at concentrations ranging from 0.002 to 0.032 micrograms/ml showed a concentration-related positive response in this assay.
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PMID:A genetic assay for aneuploidy: quantitation of chromosome loss using a mouse/human monochromosomal hybrid cell line. 305 Apr 92

6-Thio-3-deazaguanine (TDG), a relatively new purine antimetabolite, exhibits significant antitumor activity against a variety of experimental animal tumor models including C3H mammary adenocarcinoma, Lewis lung carcinoma, adenocarcinoma 755, and leukemias L1210 and P388. However, the drug was ineffective against 3-deazaguanine-resistant L1210 (both in vitro and in vivo) and CEM cells (in vitro). The resistant cells appear to lack HGPRTase activity because the extracts from these cell lines failed to convert hypoxanthine to IMP. These data indicate that TDG needs to be activated by hypoxanthine guanine phosphoribosyltransferase prior to its growth inhibitory effects. Cytotoxicity of TDG was completely reversed by hypoxanthine and inosine. TDG inhibited the synthesis of DNA and RNA equally and effectively, whereas the inhibition of protein synthesis required a prolonged drug exposure and appears to be a consequence of the inhibition of DNA and RNA synthesis. Data from these studies suggest that TDG is an effective antitumor agent, and its spectrum of antitumor activity and mechanism of action appears to be different from that of 3-deazaguanine.
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PMID:Antitumor activity and mechanism of action of 6-thio-3-deazaguanine. 381 77

Transfection of mammalian cells with genomic DNA and cloned genes is now relatively routine. However, the vast majority of studies have used rodent cells as recipients. Here we describe efficient transfection of two human cell lines, the hypoxanthine guanine phosphoribosyltransferase (HPRT)-deficient HeLa line, D98/AH-2, and the adenine phosphoribosyltransferase (APRT)-deficient HT1080 line, HTD114. D98/AH-2 cells were transfected with the pSV2-gpt plasmid of Mulligan and Berg, which contains the E. coli xanthine-guanine phosphoribosyltransferase (gpt) gene, and Gpt + transfectants were selected in HAT medium. HTD114 cells were transfected with (1) genomic hamster DNA, and ouabain resistant transfectants were selected in 5 X 10(-7)M ouabain; (2) with hamster and mouse genomic DNA, and Aprt + cells were selected in AAA medium; (3) with plasmids containing either the cloned hamster or mouse APRT genes, and Aprt + cells were selected; and (4) with phage particles containing a cloned mouse APRT gene, and Aprt + cells were selected. Transfection efficiencies ranged from 0.25 to 1.5 X 10(3) transfectants per microgram DNA, and in certain cases secondary transfections were done. Foreign DNA in recipients was detected by blot hybridization, and the expression of foreign genes was detected by cell growth in selective media and the expression of enzymes characteristic of the species of the donor DNA. The majority of transfectants showed stable expression of the transgenome.
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PMID:Plasmid, phage, and genomic DNA-mediated transfer and expression of prokaryotic and eukaryotic genes in cultured human cells. 623 89

Purine enzyme activities are usually assayed by radiochemical procedures and often TLC is part of the separation method. In screening patients with rheumatic diseases, these procedures have shown disadvantages like a relatively large coefficient of variation (C.V.) and time-instability. We describe a non-radiochemical reversed-phase HPLC micro-method with UV detection for measurement of activities of purine 5'-nucleotidase (5'NT; EC 3.1.3.5), purine nucleoside phosphorylase (PNP; EC 2.4.2.1) and hypoxanthine guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8) in human peripheral blood mononuclear cells (PBMC). The HPLC procedure is compared with the radiochemical TLC procedure by testing both with a 5'NT and a PNP assay. Reproducibility is tested with 14 healthy controls in each procedure. Short-term and long-term time-stability is tested by comparing enzyme activities measured immediately after preparation of the PBMC (week 0) with those found after freezing and storage at -20 degrees C for a maximum of 10 weeks. The HPLC procedure is preferable to the radiochemical TLC procedure because it shows significantly better reproducibility and better time-stability and in addition is non-radiochemical and less time-consuming.
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PMID:Purine enzyme activities in peripheral blood mononuclear cells: comparison of a new non-radiochemical high-performance liquid chromatography procedure and a radiochemical thin-layer chromatography procedure. 765 19


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