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)

In male BALB/c mice, a combination of individually non-lethal doses of 6-mercaptopurine and endotoxin was significantly lethal. In contrast, mice treated with phenobarbital were resistant to this lethal effect. The high levels of thioinosinic acid in mice that were treated with endotoxin contrasted significantly with the levels in phenobarbital-treated mice. On the other hand, the concentration of hypoxanthine was increased by the administration of phenobarbital and decreased by the administration of endotoxin. The sleeping time and levels of pentobarbital hydroxylase found in endotoxin-treated mice were consistent with the lethality and levels of thioinosinic acid. After mice were treated with endotoxin, their sleeping time was prolonged, which agrees with the course of the stimulatory effects of 6-mercaptopurine anabolism. However, there were no significant differences in hypoxanthine-guanine phosphoribosyltransferase. Furthermore, contrary to expectation, there were significant increases in xanthine oxidase after treatment with endotoxin. Thus, the metabolism of 6-mercaptopurine might be modified by hepatic microsomal enzyme activity.
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PMID:Effects of phenobarbital and endotoxin on the lethality and metabolism of 6-mercaptopurine in male BALB/c mice. 90 14

Pyrroxamide [N-(1-hydroxymethyl-2,3-dihydroxypropyl)-2,2,5,5-tetramethyl pyrrolidine-1-oxyl-3-carboxyamide] is a newly tested nonionic monomeric nitroxyl compound with demonstrated effectiveness for MRI contrast enhancement at doses as low as 10(-3) M. Pyrroxamide and its hydroxylamine metabolic derivative were tested in concentrations from 10(-9) to 10(-2) M with a battery of cytotoxic and mutagenic assays using mammalian Chinese hamster ovary cells. Loci-specific mutation induction was examined at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and the Na+/K+ ATPase loci, both in the presence and absence of a liver microsomal metabolic activating mixture (S-9 mix). Cell survival and induction of sister chromatid exchanges also were studied. All tests yielded negative results indicating that pyrroxamide and and hydroxylamine derivative were both noncytotoxic and nonmutagenic at the doses tested.
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PMID:Pyrroxamide, a nonionic nitroxyl spin label contrast agent for magnetic resonance imaging. Mutagenesis and cell survival. 341 40

4-Hydroxynonenal (HNE), a major product of the peroxidation of liver microsomal lipids, was examined for mutagenic activity at the hypoxanthine-guanine phosphoribosyltransferase locus in V79 Chinese hamster lung cells. At concentrations ranging from 10 to 45 microM, HNE induced a dose-dependent increase in the number of mutations to 6-thioguanine resistance, which reached the level of 4.7X baseline at the highest concentration tested.
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PMID:Mutagenicity of 4-hydroxynonenal in V79 Chinese hamster cells. 382 75

Aryl hydrocarbon (benzo[a]pyrene) hydroxylase inducibility by benzo[a]anthracene was studied in 29 somatic cell hybrid clones, developed by fusing mouse spleen or peritoneal cells from four different inbred strains with hypoxanthine phosphoribosyltransferase-deficient Chinese hamster E36 cells. Karyotype analysis plus 25 markers assigned to 16 autosomes and the X chromosome were examined. In 28 of the 29 clones, the presence or absence of inducibility is associated with the presence or absence, respectively, of mouse chromosome 17. Liver microsomal aryl hydrocarbon hydroxylase induction by 3-methylcholanthrene or benzo[a]anthracene was assessed in appropriate backcrosses with the Mus musculus molossinus, M. m. castaneus, MOR/Cv, PL/J, SM/J and DBA/2J inbred strains and in 13 NX8 recombinant inbred lines. Twenty-seven biochemical genetic markers representing all but four autosomes were tested for possible linkage with the hydroxylase inducibility, and no linkage was found. The hepatic Ah receptor was quantitated in 26 BXD recombinant inbred lines; the Ah phenotype did not match exactly any of the more than 70 genes with established strain distribution patterns representing 12 autosomes and at least five unlinked markers. It is concluded that a major gene controlling aryl hydrocarbon hydroxylase inducibility by benzo[a]anthracene is located on chromosome 17. Because there is no significant linkage with any of three biochemical markers in the upper third of the chromosome, we conclude that the inducibility gene is located in the distal 40% of mouse chromosome 17. Whether this trait represents the Ah locus, i.e., the gene encoding the cytosolic Ah receptor, will require further study.
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PMID:Aryl hydrocarbon hydroxylase induction by benzo[a]anthracene: regulatory gene localized to the distal portion of mouse chromosome 17. 654 99

Somatic cell hybrid clones were derived from the fusion of hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8)-deficient mouse cells and two different human fibroblast strains, each carrying an X chromosome-autosome translocation. One of these had an X/11 translocation [46,X,t(X;11)(p21;q13)] and the other had an X/19 translocation [46,X,t(X;19)(q22;q13)]. The structurally normal human X chromosome is the late-replicating (genetically inactive) chromosome in these two cell strains; the rearranged X chromosome is early replicating (genetically active). One primary hybrid clone carrying both the translocated X chromosome and the structurally normal X chromosome was isolated in hypoxanthine/aminopterin/thymidine medium from each of these two cell fusion experiments. These clones were then selected in medium containing 8-azaguanine to achieve the loss of the active human HPRT locus. Five subclones from the cell hybrid with the X/11 translocation failed to express two known human X-chromosome markers [glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) and phosphoglycerate kinase (PGK; EC 2.7.2.3)] but did express human microsomal steroid sulfatase (STS; sterol-sulfate sulfohydrolase, EC 3.1.6.2). Three of these were cytogenetically analyzed and found to contain a structurally normal human X chromosome but not the X/11 translocation. Two subclones were isolated in 8-azaguanine from the hybrid with the X/19 translocation. Cytogenetic analysis of these two clones showed the presence of a structurally normal human X chromosome; the X/19 translocation was not present. They did not express human G6PD, PGK, or HPRT but did express human STS. These results indicate that human STS is expressed from a locus on the inactive human X chromosome and support our earlier finding that the STS locus escapes X-inactivation in man.
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PMID:Expression of an X-linked gene from an inactive human X chromosome in mouse-human hybrid cells: further evidence for the noninactivation of the steroid sulfatase locus in man. 693 82

6-Nitrochrysene can be activated to genotoxic derivatives by two major metabolic pathways: nitroreduction to N-hydroxy-6-aminochrysene, and a combination of ring-oxidation and nitroreduction that involves the intermediate formation of trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (6-AC-1,2-dihydrodiol). The DNA adduct formed from this latter pathway was evaluated by reacting individual deoxynucleoside 5'-monophosphates with 6-AC-1,2-dihydrodiol in the presence of liver microsomal enzymes from 3-methylcholanthrene-pretreated rats. Binding was greatest to deoxyguanosine monophosphate and the major deoxyguanosine (dG) adduct co-chromatographed with the single major adduct formed from the microsome-catalyzed reaction of 6-AC-1,2-dihydrodiol with DNA. In order to characterize the mutational changes associated with the 6-AC-1,2-dihydrodiol pathway, we analyzed the mutational spectrum produced by 6-AC-1,2-dihydrodiol in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene of CHO-K1 cells. cDNA was synthesized from the RNA of 28 6-thioguanine-resistant mutants, the hprt coding region amplified by the polymerase chain reaction, and the DNA products directly sequenced. Twenty independent primary mutations were found: 12 G:C-->T:A transversions, three G:C-->C:G transversions, one G:C-->A:T transition, one A:T-->T:A transversion, two -1 frameshift mutations in sequences containing consecutive guanines, and one 11 bp deletion. All G:C basepair substitutions had the mutated dG on the non-transcribed strand and 86% of the G:C basepair substitutions had one purine 3' to the mutated dG. The pattern of 6-AC-1,2-dihydrodiol-induced basepair substitutions was distinct from the pattern observed in solvent control mutants. These results are consistent with the formation of a promutagenic dG adduct from a metabolite of 6-AC-1,2-dihydrodiol.
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PMID:Trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene is metabolized to form a major adduct with deoxyguanosine and produces mutations in the hprt gene of Chinese hamster ovary cells at G:C basepairs. 822 62

Dimethacrylate derivatives are used as monomers to polymerize dental composite materials and for a great variety of other industrial resins. Occupational exposure is likely in various ways because of the many areas of methacrylate application. Here, the mutagenicity of the monomers, bisphenol A-diglycidyl dimethacrylate (Bis-GMA), urethane dimethacrylate (UDMA), triethylene glycol dimethacrylate (TEGDMA), Bisphenol A (BPA), glycidyl methacrylate (GMA), methyl methacrylate (MMA), and 2-hydroxyethyl methacrylate (HEMA) was studied in a bacterial (Ames test) and a mammalian gene mutation assay (V79/HPRT assay). Mutagenicity was determined in different Salmonella typhimurium strains (TA97a, TA98, TA100, TA102) and in V79 cells in the presence and in the absence of a metabolically active microsomal fraction from rat liver (S9). No mutagenic effects were observed with Bis-GMA and UDMA, methyl methacrylate, 2-hydroxyethyl methacrylate and bisphenol A. Glycidyl methacrylate (GMA) was mutagenic in a dose-dependent manner in three Salmonella tester strains. The number of mutants was increased by a factor of 2 to 3 with strains TA97a and TA102 in the absence of S9. Moreover, the numbers of mutants induced in S. typhimurium TA100 were about 8-fold higher than in solvent controls. GMA also induced an increase of mutants in V79 cells in the absence of S9. However, GMA was inactivated by microsomal enzymes. Triethylenglycol dimethacrylate (TEGDMA) was not mutagenic in any S. typhimurium. In contrast, the compound induced a dose-dependent rise in mutant frequencies in V79 cell cultures. It is concluded that TEGDMA acted through a clastogenic mechanism which is not detected by Ames tester strains.
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PMID:The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells. 971 Dec 68

Synaptosomal fractions from rat brain have been analyzed with semi-quantitative RT-PCR methods to determine their content of mRNAs coding for presynaptic, postsynaptic, glial, and neuronal proteins. Each mRNA was determined with reference to the standard HPRT mRNA. In our analyses, mRNAs were considered to be associated with synaptosomes only if their relative amounts were higher than in microsomes prepared in a polysome stabilizing medium, rich in Mg(++) and K(+) ions, or in the homogenate. According to this stringent criterion, the following synaptosomal mRNAs could not be attributed to microsomal contamination and were assumed to derive from the subcellular structures known to harbor their translation products, i.e. GAT-1 mRNAs from presynaptic terminals and glial processes, MAP2 mRNA from dendrites, GFAP mRNA from glial processes, and TAU mRNA from neuronal fragments. This interpretation is in agreement with the involvement of extrasomatic mRNAs in local translation processes.
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PMID:Messenger RNAs in synaptosomal fractions from rat brain. 1175 73