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)

Studies of mutation at the hypoxanthine phosphoribosyl transferase (hrpt) locus in human T-cells have the potential to elucidate the molecular basis of in vivo mutagenesis, reveal exposure dependent changes in ther background frequency of mutation, and provide knowledge on individual sensitivity. Styrene exposed lamination workers in Bohemia showed a significantly higher frequency of hprt mutant cells than Swedish control populations studied simultaneously. In a study of 47 healthy, non-smoking male bus maintenance workers exposed to diesel exhausts, soot and oil, and 22 unexposed controls, a significant correlation (P = 0.008) was obtained between the levels of aromatic DNA adducts and frequencies of hprt-mutant T-cells. In the group of workers with the highest exposure, subjects with glutathione S-transferase (GSTM1) deficiency showed significantly higher (P < 0.05) frequency of hprt mutant T-cells than GSTM1-positive subjects. The highest adduct levels were found in subjects with the combined genotype of GSTM1 and NAT2 deficiency (GSTM1-negative slow acetylators). These results indicate that GSTM1 and NAT2 genotypes may play a role in determining the individual levels of hprt mutation and DNA adducts. Using PCR-based screening methods, hprt mutations have been classified in 462 T-cell clones from 43 subjects in this study population. Deletions were found in 3% of the mutants, coding errors in 81% and splice mutations in 17%. Transitions and transversions were equally common, and all types of base substitutions were detected.
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PMID:Analysis of mutation at the hprt locus in human T lymphocytes. 859 72

We evaluated our data on the occupational exposure to styrene in lamination workers. The battery of parameters included markers of external and internal exposure and biomarkers of biological effects and susceptibility. DNA repair capacities have been determined in both exposed and control groups. Styrene workplace concentration significantly correlated with styrene concentration in blood, exhaled air and urinary mandelic acid. Haemoglobin and O(6)-styrene oxide (SO)-guanine DNA adducts were significantly higher in exposed subjects as compared to controls and correlated with exposure parameters. In styrene-exposed workers 1-SO-adenine DNA adducts were detected (2.6 per 10(9) dNp), while in controls these adducts were below the detection limit. 1-SO-adenine adduct levels were affected by both acute and cumulative exposure (P=0.001, F=86.0 and P=0.017, F=59.0, respectively) and associated with cytochrome P450 2E1 (CYP2E1) polymorphisms (R(2)=0.442). Mutant frequencies (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus appeared to accumulate with exposure over time and were associated with glutathione S-transferase P1 (GSTP1) polymorphism. DNA repair capacity increased with the exposure, except for the group exposed to the highest styrene concentration. In this particular group, increased DNA repair capacity to remove oxidative DNA damage was found.
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PMID:The role of various biomarkers in the evaluation of styrene genotoxicity. 1289 75

A multiinstitutional, transitional epidemiologic study was conducted with a worker population in the Czech Republic to evaluate the utility of a continuum of non-disease biological responses as biomarkers of exposure to 1,3-butadiene (BD)* in an industrial setting. The study site included two BD facilities in the Czech Republic. Institutions that collaborated in the study were the University of Vermont (Burlington, Vermont, USA); the Laboratory of Genetic Ecotoxicology (Prague, the Czech Republic); Shell International Chemicals, BV (Amsterdam, The Netherlands); the University of North Carolina at Chapel Hill (Chapel Hill, North Carolina, USA); University of Texas Medical Branch at Galveston (Galveston, Texas, USA); Leiden University (Leiden, The Netherlands); and the Health and Safety Laboratory (Sheffield, United Kingdom). Male volunteer workers (83) participated in the study: 24 were engaged in BD monomer production, 34 in polymerization activities, and 25 plant administrative workers served as unexposed control subjects. The BD concentrations experienced by each exposed worker were measured by personal monitor on approximately ten separate occasions for 8-hour workshifts over a 60-day exposure assessment period before biological samples were collected. Coexposures to styrene, benzene, and toluene were also measured. The administrative control workers were considered to be a homogeneous, unexposed group for whom a series of 28 random BD measurements were taken during the exposure assessment period. Questionnaires were administered in Czech to all participants. At the end of the exposure assessment period, blood and urine samples were collected at the plant; samples were. fractionated, cryopreserved, and kept frozen in Prague until they were shipped to the appropriate laboratories for specific biomarker analysis. The following biomarkers were analyzed: * polymorphisms in genes involved in BD metabolism (Prague and Burlington); * urinary concentrations of 1-hydroxy-2-(N-acetylcysteinyl)-3-butene and 2-hydroxy-1-(N-acetylcysteinyl)-3-butene (M2 [refers to an isomeric mixture of both forms]) (Amsterdam); * urinary concentrations of 1,2-dihydroxy-4-(N-acetylcysteinyl)-butane (M1) (Amsterdam); * concentrations of the hemoglobin (Hb) adducts N-(1-[hydroxymethyl]-2-propenyl)valine and N-(2-hydroxy-3-butenyl)valine (HBVal [refers to an isomeric mixture of both forms]) (Amsterdam); * concentrations of the Hb adduct N-(2,3,4-trihydroxybutyl)valine (THBVal) (Chapel Hill); * T cell mutations in the hypoxanthine phosphoribosyltransferase (HPRT) gene (autoradiographic assay in Galveston with slide review in Burlington; cloning assay in Leiden with mutational spectra determined in Burlington); and * chromosomal aberrations by the conventional method and by fluorescence in situ hybridization [FISH]), and cytogenetic changes (sister chromatid exchanges [SCEs] (Prague). All assay analysts were blinded to worker and sample identity and remained so until all work in that laboratory had been completed and reported. Assay results were sent to the Biometry Facility in Burlington for statistical analyses. Analysis of questionnaire data revealed that the three exposure groups were balanced with respect to age and years of residence in the district, but the control group had significantly more education than the other two groups and included fewer smokers. Group average BD exposures were 0.023 mg/m3 (0.010 ppm) for the control group, 0.642 mg/m3 (0.290 ppm) for the monomer group, and 1.794 mg/m3 (0.812 ppm) for the polymer group; exposure levels showed considerable variability between and within individuals. Styrene exposures were significantly higher in the polymer group than in the other two groups. We found no statistically significant differences in the distributions of metabolic genotypes over the three exposure groups; genotype frequencies were consistent with those previously reported for this ethnic and national population. Although some specific genotypes were associated with quantitative differences in urinary metabolite concentrations or Hb adduct dose-response characteristics, none indicated a heightened susceptibility to BD. Concentrations of both the M2 and M1 urinary metabolites and both the HBVal and THBVal Hb adducts were significantly correlated with group and individual mean BD exposure levels; the Hb adducts were more strongly correlated than the urinary metabolites. By contrast, no significant relations were observed between BD exposures and HPRT gene mutations (whether determined by the auto-radiographic or the cloning method) or any of the cytogenetic biomarkers (whether determined by the conventional method or FISH analysis). Neither the mutational nor the cytogenetic responses showed any association with genotypes. The molecular spectrum of HPRT mutations in BD-exposed workers showed a high frequency of deletions; but the same result was found in the unexposed control subjects, which suggests that these were not due to BD exposure. This lack of association between BD exposures and genetic effects persisted even when control subjects were excluded from the analyses or when we conducted regression analyses of individual workers exposed to different levels of BD.
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PMID:Biomarkers in Czech workers exposed to 1,3-butadiene: a transitional epidemiologic study. 1293 46