Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ammonium metavanadate yielded a dose-dependent increase in mutation frequency at the V79 hprt locus following a 24-h exposure period in serum-free F12 medium. Vanadate also increased the mutation frequency of V79 cells by exposure of cells in salts-glucose medium, but these effects were not as striking, or as dose-dependent as they were in serum-free F12 medium. Ammonium metavanadate enhanced the mutation frequency in a V79 variant containing a transfected bacterial gpt gene. These cells are known to be more responsive to oxidative type mutations, and to mutations involving deletions. Although the absolute level of mutations was greater in these cells with ammonium metavanadate, so was the background, and these cells did not exhibit an enhanced mutagenic response to vanadate when compared to the wild-type V79 cells. The vanadate results were compared to a positive control potassium chromate, which exhibited a dose-dependent increase in mutation frequency. Ammonium metavanadate induced DNA-protein crosslinks formation in both Chinese hamster ovary and human MOLT4 cells, and the role of these relatively unrepaired genetic lesions in the mutations produced by vanadate and chromate are discussed.
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PMID:Forward mutations and DNA-protein crosslinks induced by ammonium metavanadate in cultured mammalian cells. 138 66

We have studied the mutagenicity and toxicity of physical and chemical agents in the Chinese hamster ovary (CHO) cell line K1-BH4 and its transformant, AS52. The AS52 cells lack the normal X-linked mammalian hypoxanthine-guanine phosphoribosyltransferase (hprt) gene but instead contain a single autosomally integrated copy of the bacterial equivalent, the xanthine-guanine phosphoribosyltransferase (gpt) gene. We found that X-rays and neutrons appear to be equitoxic to both cell types; however, these physical agents are approximately 10 times more mutagenic to the gpt gene of AS52 cells than to the hprt gene of K1-BH4 cells. We reasoned that if reactive oxygens were to mediate the mutagenic effects of both radiomimetic chemicals and radiation, then reactive oxygen-producing chemicals, such as streptonigrin and bleomycin, and oxidizing agents such as potassium superoxide and hydrogen peroxide, would exhibit similar levels of toxicity but different frequencies of mutants when assayed with the two cell lines. Our experiments fulfill such predictions. We postulate that the apparent hypermutability of AS52 cells probably results from a higher recovery of multi-locus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants. Preliminary studies, using Southern blot and the polymerase chain reaction to analyze the mutational spectrum of the mutants, support our hypothesis that reactive oxygens induce deletion mutations in mammalian cells.
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PMID:Molecular analysis of reactive oxygen-species-induced mammalian gene mutation. 197 50

Mammalian cells in culture have been used to study the genetic effects of physical and chemical agents. We have used Chinese hamster ovary (CHO) cells, clone K1-BH4, to quantify mutations at the X-linked, large (35 kb) hypoxanthine-guanine phosphoribosyltransferase (hprt) locus (the CHO/HPRT assay) induced by environmental agents. By transfecting an hprt-deletion mutant CHO cell line with the plasmid vector pSV2gpt, we isolated a transformant, AS52. AS52 cells carry a single functional copy of an autosomal, small (456 bp) xanthine-guanine phosphoribosyltransferase (gpt) gene (the bacterial equivalent of the mammalian hprt gene; AS52/GPT assay). We found that ionizing radiations such as X-rays and neutrons and oxidative genotoxic chemicals such as Adriamycin, bleomycin, hydrogen peroxide, and potassium superoxide are much more mutagenic to the gpt gene in AS52 cells than to the hprt locus in K1-BH4 cells. The hypermutability of the gpt gene probably results from a higher recovery of multilocus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants. These results demonstrate that the use of the hprt locus alone could lead to an underestimate of the genetic risk of these agents. Analyses of the mutation spectrum using a polymerase chain reaction-based deletion screening and DNA sequencing procedure showed that a high proportion of HPRT- and GPT- mutants induced by X-rays carry deletion mutations. Thus, both the mutant frequency and mutation spectrum need to be considered in assessing the genetic risk of ionizing radiation and oxidative genotoxic chemicals.
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PMID:Quantitative and molecular analyses of genetic risk: a study with ionizing radiation. 814 20

The roles of two adjacent genes in the Staphylococcus aureus chromosome with functions in starvation survival and the response to stressful conditions have been characterized. One of these, hprT, encoding a hypoxanthine-guanine phosphoribosyltransferase homologue, was initially identified in a transposon mutagenesis screen. Mutation of hprT affects starvation survival in amino-acid-limiting conditions and the ability of S. aureus to grow in high-salt concentrations. Downstream of hprT is ftsH, which encodes a membrane-bound, ATP- and Zn(2+)-dependent 'AAA'-type protease. Mutation of ftsH in S. aureus leads to pleiotropic defects including slower growth, sensitivity to salt, acid, methyl viologen and potassium tellurite stresses, and reduced survival in amino-acid- or phosphate-limiting conditions. Both hprT-lacZ and ftsH-lacZ gene fusions are expressed maximally in the post-exponential phase of growth. Although secretion of exoproteins is not affected, an ftsH mutant is attenuated in a murine skin lesion model of pathogenicity.
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PMID:Role of the hprT-ftsH locus in Staphylococcus aureus. 1476 15

A 30-year-old man was referred for investigation and management of hyperuricaemia. History included recurrent nephrolithiasis and chronic gout with poor response to medical management. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme activity was investigated and found to be deficient confirming the diagnosis of Lesch-Nyhan disease. Hyperuricaemia was treated with allopurinol. To prevent nephrolithiasis, the patient was instructed to avoid dehydration and aim for a minimum urine output of 2 L/day. Urinary alkalinisation with potassium citrate was started. The patient was referred for genetic counselling. This case discusses the genetics, pathophysiology, clinical manifestations, diagnosis and management of HGPRT deficiency.
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PMID:Late diagnosis of Lesch-Nyhan disease variant. 2432 40