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João Paulo Teixeira,
Jorge Gaspar,
Patrícia Coelho,
Carla Costa,
Susana Pinho-Silva,
Solange Costa,
Susana Da Silva,
Blanca Laffon,
Eduardo Pásaro,
José Rueff, Peter Farmer
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ABSTRACT: Styrene is a commercially important chemical widely used in the manufacture of synthetic rubber, resins, polyesters and plastics. The highest levels of human exposure to styrene occur during the production of reinforced plastic products. The objective of this work was to evaluate both DNA and cytogenetic damage in styrene-exposed workers, analysing only non-smoker individuals. Environmental levels of styrene and urinary concentrations of mandelic and phenylglyoxylic acids were determined, and genetic damage was studied by means of micronucleus (MN) test, sister chromatid exchanges (SCEs) and comet assay. Fifty-two fibreglass-reinforced plastics workers and 54 controls took part in the study. The mean air concentration of styrene in the breathing zone of workers exceeded the threshold limit value, and 24 workers exceeded the biological exposure index. A strong and significant correlation was found between styrene environmental concentrations and urinary metabolites. Higher SCE rate (P<0.01) was observed in exposed workers than in controls. Besides, significant correlations were obtained for SCE rate with both environmental and internal exposure parameters (r=0.496, P<0.01 and r=0.511, P<0.01, respectively). Results from MN test and comet assay showed slight and non-significant increases related to the exposure. Our data seem to support previous studies reporting genotoxicity associated with occupational exposure to styrene, excluding the confounding influence of smoking, although caution must be taken in the interpretation of these results since the significance of an increase in SCE rate is still unclear.
Mutagenesis 11/2010; 25(6):617-21. · 3.18 Impact Factor
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Camille Ragin,
Aerie Minor,
Antonio Agudo, Peter Farmer,
Seymour Garte,
Carlos Gonzales,
Ivan Kalina,
Giuseppe Matullo,
Todor Popov,
Domenico Palli,
Marco Peluso,
Fulvio Ricceri,
Radim Sram,
Paolo Vineis,
Emanuela Taioli
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ABSTRACT: There is some evidence that dietary components that are rich in antioxidant and vitamins are inversely associated with DNA adduct levels induced by environmental carcinogens such as polycyclic aromatic hydrocarbons, although the epidemiologic data are inconsistent. This study addresses the association between vitamins, DNA adducts and smoking.
A combined analysis of individual data on the association between bulky DNA adducts and dietary vitamins was conducted. A Medline search was performed to identify studies on healthy subjects in which smoking and vitamins intake information were available, and bulky DNA adducts were measured in peripheral blood with 32P-postlabelling. Eight published studies met the eligibility criteria, and individual data from 7 data sets including 2758 subjects were obtained. GSTM1 and GSTT1 were also available on all the subjects.
Vitamin E was inversely significantly associated with DNA adducts after adjustment for possible confounding factors. Vitamins A and C were not independent predictors of DNA adducts. A stratified analysis showed that vitamin A had a significant inverse association with DNA adducts in ever smokers only.
This result is relevant to planning any future chemo-preventive interventions directed to high risk subgroups of the population, for cancer prevention.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/2010; 705(2):77-82. · 2.85 Impact Factor
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ABSTRACT: Human metabolism of benzene involves pathways coded for by polymorphic genes. To determine whether the genotype at these loci might influence susceptibility to the adverse effects of benzene exposure, 208 Bulgarian petrochemical workers and controls, whose exposure to benzene was determined by active personal sampling, were studied. The frequency of DNA single-strand breaks (DNA-SSB) was determined by alkaline elution, and genotype analysis was performed for five metabolic loci. Individuals carrying the NAD(P)H:quinone oxidoreductase 1 (NQO1) variant had significantly twofold increased DNA-SSB levels compared to wild-type individuals. The same result was observed for subjects with microsomal epoxide hydrolase (EPHX) genotypes that predict the fast catalytic phenotype. Deletion of the glutathione S-transferase T1 (GSTT1) gene also showed a consistent quantitative 35-40% rise in DNA-SSB levels. Neither glutathione S-transferase M1 (GSTM1) nor myeloperoxidase (MPO) genetic variants exerted any effect on DNA-SSB levels. Combinations of two genetic polymorphisms showed the same effects on DNA-SSB as expected from the data on single genotypes. The three locus genotype predicted to produce the highest level of toxicity, based on metabolic pathways, produced a significant 5.5-fold higher level of DNA-SSB than did the genotype predicted to yield the least genotoxicity.
Journal of Toxicology and Environmental Health Part A 02/2008; 71(22):1482-9. · 1.83 Impact Factor
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ABSTRACT: A useful approach for studies on the mechanisms of genetic variation in cancer susceptibility is to use intermediary biochemical endpoints with mechanistic relevance to the genes under study. We examined the effects of individual genotype at seven metabolic gene loci on a marker of oxidative DNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine, in people exposed to polycyclic aromatic hydrocarbons (PAH) from three Central European cities. The GSTT1 homozygous deletion variant was associated with a significant protective effect for exposure to total PAHs and to eight specific PAHs, although the magnitude and significance of the effect varied among these compounds. Categorical sensitivity analysis was used to determine that the frequency of the GSTT1 deletion was significantly higher in people who proved to be more resistant to the DNA damaging effects of PAH exposure than in people who were the most sensitive. There is a growing literature on the protective effect of GSTT1 deletion in both disease and intermediary endpoints related to environmental carcinogenesis. The mechanism for this effect might be related to specific PAH substrate specificities, or could be related to other functions of GSTT1 gene in oxidative stress induced damage pathways.
International Journal of Cancer 07/2007; 120(11):2499-503. · 5.44 Impact Factor
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ABSTRACT: Biomarkers of benzene exposure and effect were evaluated in 158 Bulgarian petrochemical workers and 50 matched controls. Air exposures to benzene averaged about 1.8 ppm, for workers and 0.02 ppm for controls. Urinary trans,trans-muconic acid, and S-phenylmuconic acid, showed dose response relationships with benzene air exposure. The dose response curve for DNA single strand breaks (SSB), but not for the metabolites, showed a saturation effect. NQO1 genotype had a significant effect on SSB. We conclude that the pathways for these metabolites may be distinct from those involved in some forms of genotoxic damage induced by benzene.
Chemico-Biological Interactions 06/2005; 153-154:247-51. · 2.46 Impact Factor
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Silvia Fustinoni,
Marina Buratti,
Laura Campo,
Antonio Colombi,
Dario Consonni,
Angela C Pesatori,
Matteo Bonzini, Peter Farmer,
Seymour Garte,
Federico Valerio,
Domenico F Merlo,
Pier A Bertazzi
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ABSTRACT: This research compared the capability of urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid (S-PMA) and benzene excreted in urine (U-benzene) to monitor low benzene exposure and evaluated the influence of smoking habit on these indices. Gasoline attendants, urban policemen, bus drivers and two groups of referents working in two large Italian cities (415 people) were studied. Median benzene exposure was 61, 22, 21, 9 and 6 microg/m3, respectively, with higher levels in workers than in referents. U-benzene, but not t,t-MA and S-PMA, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to five-fold higher in smokers compared to non-smokers. In conclusion, in the range of investigated benzene exposure (<478 microg/m3 or <0.15 ppm), the smoking habit may be regarded as a major source of benzene intake; among the study indices, U-benzene is the marker of choice for the biological monitoring of occupational and environmental exposure.
Chemico-Biological Interactions 05/2005; 153-154:253-6. · 2.46 Impact Factor
