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

Phosphoribosylpyrophosphate in amounts as low as 25 pmol could be reliably and economically measured with a CO2-releasing radioenzymatic assay when appropriate technical modifications were introduced. The concentration of commercially available phosphoribosylpyrophosphate used for reference standards was ascertained by a method based on the utilization of phosphoribosylpyrophosphate by hypoxanthine catalyzed by hypoxanthine phosphoribosyltransferase from red blood cell lysates. The addition of inorganic phosphate increased intracellular phosphoribosylpyrophosphate levels in HL-60 cell lysates and can be used to amplify low levels of phosphoribosylpyrophosphate. This phosphoribosylpyrophosphate assay amplified by inorganic phosphate has been developed to assay perturbations in the purine biosynthetic nucleotide pathway in response to various chemotherapeutic agents, such as anti-folates, or as a result of folate deficiency.
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PMID:Modified phosphoribosylpyrophosphate (PRPP) radioenzymatic assay: increased sensitivity, technical simplification and new applications. 243 41

To investigate the interaction of folate deficiency and alkylating agents in vivo, weanling Fischer 344 rats were maintained for 5 weeks on a folate replete, moderately folate deficient, or a severely folate deficient diet. Mutant frequencies at the HPRT locus in splenic lymphocytes were 1.2+/-0.6, 1.9+/-1.1, and 6.4+/-4.0 x 10(-6), respectively (P < 0.01). N-nitroso-N-ethylurea (ENU), 100 mg/kg body weight, was much more mutagenic with progressive folate deficiency (5.0+/-2.4 vs. 16.2+/-7.3 vs. 39.2+/-21.0 x 10(-6)), suggesting a synergistic interaction (P << 0.01). Neither moderate nor severe folate deficiency significantly enhanced the mutagenic effects of cyclophosphamide, 50 mg/kg body weight (18.0+/-7.9 vs. 6.0+/-2.8 vs. 28.5+/-28.2 x 10(-6)). The number of cloning cells/ spleen were reduced 68% in moderately folate deficient rats and by 87% in severely deficient animals (P < 0.05). The combination of folate deficiency and cyclophosphamide reduced the total number of cloning cells further, but ENU alone, or in combination with folate deficiency, did not. These findings indicate that folate deficiency increases the risk of somatic mutations and is lymphocytotoxic in rats. Folate deficiency enhances the mutagenic but not the lymphotoxic effects of ENU, while it increases the lymphotoxic but not the mutagenic activity of cyclophosphamide. Correction of folate deficiency may decrease the immunologic and genetic damage caused by some alkylating agents.
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PMID:Nutritional folate deficiency augments the in vivo mutagenic and lymphocytotoxic activities of alkylating agents. 970 96

Folic acid deficiency acts synergistically with alkylating agents to increase genetic damage at the HPRT locus in Chinese hamster ovary cells in vitro and in rat splenocytes in vivo. The present studies extend these observations to human cells and, in addition, investigate the role of p53 activity on mutation induction. The human lymphoblastoid cell lines TK6 and WTK1 are derived from the same parental cell line (WI-L2), but WTK1 expresses mutant p53. Treatment of folate-replete or deficient WTK1 and TK6 cells with increasing concentrations (0-50microg/ml) of ethyl methanesulfonate (EMS) resulted in significantly different HPRT mutation dose-response relationships (P<0.01), indicating that folate deficiency increased the EMS-induced mutant frequency in both cell lines, but with a greater effect in TK6 cells. Molecular analyses of 152 mutations showed that the predominant mutation (65%) in both cell types grown in the presence or absence of folic acid was a G>A transition on the non-transcribed strand. These transitions were mainly at non-CpG sites, particularly when these bases were flanked 3' by a purine or on both sides by G:C base pairs. A smaller number of G>A transitions occurred on the transcribed strand (C>T=14%), resulting in 79% total G:C>A:T transitions. There were more genomic deletions in folate-deficient (15%) as compared to replete cells (4%) of both cell types. Mutations that altered RNA splicing were common in both cell types and under both folate conditions, representing 33% of the total mutations. These studies indicate that cells expressing p53 activity exhibit a higher rate of mutation induction but are more sensitive to the toxic effects of alkylating agents than those lacking p53 activity. Folate deficiency tends to reduce toxicity but increase mutation induction after EMS treatment. The p53 gene product did not have a major influence on the molecular spectrum after treatment with EMS, while folate deficiency increased the frequency of deletions in both cell types.
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PMID:The effect of folate deficiency on the cytotoxic and mutagenic responses to ethyl methanesulfonate in human lymphoblastoid cell lines that differ in p53 status. 1116 26