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)

The influence of the dietary antioxidants vitamin C, alpha- and beta-carotene, lycopene, lutein/zeaxanthin, phytofluene, beta-cryptoxanthin, retinol and alpha- and gamma-tocopherol on the hypoxanthine phosphoribosyltransferase (hprt) mutant frequency in human peripheral T lymphocytes was investigated. Twenty-five male non-smokers and 27 male smokers in the age range 50-59 years were recruited. Smokers showed a significantly higher mutant frequency compared with non-smokers (X1.5, P < 0.01). In addition, there was a significant positive relationship between hprt mutant frequency and the number of cigarettes that individuals reported smoking daily (P < 0.01). Smokers showed significantly lower levels of plasma vitamin C and the carotenoid alpha-carotene than non-smokers (P < 0.01 and P < 0.05 respectively). Both hprt mutant frequency and lymphocyte plating efficiency were weakly inversely associated with plasma vitamin C levels (P < 0.07 and P < 0.06 respectively) suggesting that vitamin C may be protective against mutation at the hprt locus. This relationship was markedly stronger in smokers (P < 0.01).
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PMID:The influence of smoking and diet on the hypoxanthine phosphoribosyltransferase (hprt) mutant frequency in circulating T lymphocytes from a normal human population. 766 69

Epidemiological studies have demonstrated protective effects of vegetables and fruit on risk of cancer, but underlying mechanisms remain unclear. Intervention studies have in some cases contradicted previous epidemiological evidence, e.g. for beta-carotene supplementation and lung cancer, emphasizing the need for mechanistic data. We assessed in vivo mutagenic effects of several dietary items using the HPRT (hypoxanthine-guanine phosphoribosyl transferase) gene assay with T-lymphocytes from 312 individuals (158 lung cancer cases, 154 population controls), who provided information on diet and smoking habits. HPRT mutant frequency (MF) was significantly decreased in relation to intake of vegetables, citrus fruits and berries, respectively, as well as calculated vitamin C intake from diet. There was a significant U-shaped association with dietary carotenoid intake, with lowest MF near population average carotenoid intakes and higher mutation frequencies both at low and high intakes, and a similar borderline significant association was observed for beta-carotene. Our study is consistent with known diet-cancer associations and provides novel human in vivo mechanistic support for a cancer-protective effect of vegetables and fruit by modulation of somatic mutagenesis. Our results also provide support for the increase in lung cancer risk observed particularly in smokers in studies of beta-carotene supplementation.
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PMID:Dietary fruit and vegetables protect against somatic mutation in vivo, but low or high intake of carotenoids does not. 1272 97

It has been reported that X-ray induced HPRT- mutation in cultured human cells is prevented by ascorbate added after irradiation. Mutation extinction is attributed to neutralization by ascorbate, of radiation-induced long-lived radicals (LLR) with half-lives of several hours. We here show that post-irradiation treatment with ascorbate (5 mM added 30 min after radiation) reduces, but does not eliminate, the induction of CD59- mutants in human-hamster hybrid A(L) cells exposed to high-LET carbon ions (LET of 100 KeV/microm). RibCys, [2(R,S)-D-ribo-1',2',3',4'-Tetrahydroxybutyl]-thiazolidene-4(R)-ca riboxylic acid] (4 mM) gave a similar but lesser effect. The lethality of the carbon ions was not altered by these chemicals. Preliminary data are presented that ascorbate also alters the spectrum of CD59- mutations induced by the carbon beam, mainly by reducing the incidence of small mutations and mutants displaying transmissible genomic instability (TGI), while large mutations are unaffected. Our results suggest that LLR are important in initiating TGI.
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PMID:Ascorbate, added after irradiation, reduces the mutant yield and alters the spectrum of CD59- mutations in A(L) cells irradiated with high LET carbon ions. 1279 67

Miazaki, Watanabe, Kumagai and their colleagues reported that induction of HPRT(-) mutants by X-rays in cultured human cells was prevented by ascorbate added 30min after irradiation. They attributed extinction of induced mutation to neutralization by ascorbate of radiation-induced long-lived mutagenic radicals (LLR), found using spectroscopy to have half-lives of minutes or hours. We find that post-irradiation treatment with ascorbate reduces, but does not eliminate, induction of CD59(-) mutants in human-hamster hybrid A(L) cells exposed to high-LET carbon-ions (LET of 100KeV/microm). A(L) cells contain a standard set of Chinese hamster ovary (CHO) chromosomes and a single copy of human chromosome 11 containing the CD59 gene which encodes the CD59 cell surface antigen, a convenient marker for mutation. RibCys [2(R, S)-D-ribo-(1',2',3',4'-tetrahydroxybutyl)thiazolidine-4(R)-carboxylic acid] a 'prodrug' of l-cysteine which also scavenges LLR, had a similar but lesser effect on induced mutation. DMSO, which scavenges classical radicals like H* and OH* but not LLR, also reduced mutation, but only when it was present during irradiation. The lethality of carbon-ions was not altered by ascorbate, RibCys no matter when added. Post-radiation addition of ascorbate and RibCys also affected the quality of CD59(-) mutations induced by carbon-ions. The major change in mutant spectra was a reduction in the prevalence of small, intragenic mutations (mutations not detected by PCR) and in the prevalence of unstable, complicated mutants, which display high levels of persistent chromosomal instability. Thus, ascorbate and RibCys may suppress some kinds of mutations induced by ionizing radiation including those displaying aspects of radiation-induced genomic instability. Countering the effects of both classical radicals and LLR may be important in preventing genetic diseases.
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PMID:A role for long-lived radicals (LLR) in radiation-induced mutation and persistent chromosomal instability: counteraction by ascorbate and RibCys but not DMSO. 1522 98