Occupational exposure to polycyclic aromatic hydrocarbons in German industries: association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms.
ABSTRACT A cross-sectional study was conducted in 170 German workers exposed to polycyclic aromatic hydrocarbons (PAH) to investigate the role of 11 polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, GSTM1, GSTT1, and GSTP1 in the association between occupational exposure to PAH and urinary PAH metabolites. Polymorphisms were genotyped with real-time PCR. Exposure to 16 PAH was measured by personal air sampling. Urinary concentrations of 1-hydroxypyrene (1-OHP) and the sum of 1-, 2+9-, 3-, and 4-hydroxyphenanthrenes (OHPhe) were determined post-shift. Urinary 1-OHP and OHPhe correlated significantly with exogenous pyrene (Spearman r=0.52, p<0.0001) and phenanthrene (Spearman r=0.72, p<0.0001), respectively. ANCOVA was applied to investigate potential predictors of the metabolite levels. Current smoking and type of industry turned out to be predictors of 1-OHP but not of OHPhe. CYP1A1 3801TC carriers showed 1.6-fold higher OHPhe levels than 3801TT carriers (p=0.03). EPHX1 113HH was associated with higher and 139RR with lower metabolite levels when compared with the corresponding reference genotypes (113YY; 139HH). In comparison to GSTP1 114AA, carriers of the V allele had 1.5-fold higher 1-OHP (p=0.03) and 2-fold higher OHPhe concentrations (p=0.001). OHPhe turned out to be also a suitable biomarker of occupational PAH exposure. The association with ambient PAH exposure and the influence of polymorphisms was more pronounced for OHPhe.
- SourceAvailable from: Gemma Castano-Vinyals[show abstract] [hide abstract]
ABSTRACT: Metabolites of pyrene and DNA adducts have been used as biomarkers of high level exposure to polycyclic aromatic hydrocarbons (PAHs). A systematic review was performed to evaluate whether these biomarkers are also valid markers of low level environmental exposure to PAHs. Thirty five studies were identified with more than 10 subjects that evaluated environmental air pollution to PAHs in relation to metabolites of PAHs, mainly hydroxypyrene (1-OHP), PAH-DNA adducts, or protein adducts. PAH metabolites and, to a less extent, PAH-DNA adducts correlated well at the group level with exposure to B(a)P even at low levels of air pollution. The use of these biomarkers should be more widely implemented in combination with more traditional techniques for the assessment of general population exposure to PAHs from ambient air pollution.Occupational and environmental medicine 05/2004; 61(4):e12. · 3.64 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Glutathione and glutathione-dependent enzymes are ubiquitously distributed through nature. These enzyme systems appear to have evolved to protect cells from toxic and mutagenic environmental chemicals. There is now unequivocal evidence demonstrating that these enzymes play a role in chemical resistance in a variety of phylogeny including, bacteria, plants and insects. There is also increasing circumstantial, as well as genetic evidence which indicates that these enzymes are also a determinant in the sensitivity of tumor cells to anticancer drugs, particularly alkylating agents and those drugs whose toxic effects are mediated by free radicals. In this review some of the experimental data which leads to these conclusions is discussed.Pharmacology [?] Therapeutics 02/1991; 51(1):139-54. · 7.79 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The interest of the Commission for the Investigation of Health Hazards of Chemical Compounds in Work Area of the German Science Foundation in practical, sensitive and specific methods for monitoring the limit values led to the establishment of the working group Analytical Chemistry in 1969. A loose-leaf collection Analysen in biologischem Material and 3 volumes of an English edition have since been published. In the meantime the German edition of Analyses in biological materials has been supplemented ten times, including 100 methods for the measurement of about 170 parameters; the English edition is in 3 volumes with 45 selected methods. The volumes include only standard operational procedures that are suitable for routine use. The reliability of the analytical procedures is defined and checked for these reasons and because they satisfy the requirements of statistical quality control. The analytical methods published by the Working Group Analytical Chemistry are recommended by pertinent guidelines and regulations for use in Germany.Fresenius Journal of Analytical Chemistry 05/1993; 346(6):828-829.