Genetic polymorphism of drug-metabolizing enzymes and styrene-induced DNA damage
ABSTRACT A cross-sectional study was carried out on 48 workers exposed to styrene and 14 unexposed healthy controls in order to investigate the genotoxic potential of styrene exposure. DNA damage was assessed in peripheral blood leukocytes (WBCs) by the comet assay. Polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and the gene encoding microsomal epoxide hydrolase (EPHX) were characterized to assess their possible modifying role in styrene metabolism and subsequent DNA damage. Exposed workers showed significantly higher levels of DNA damage compared to controls. Among workers, the GSTM1 and GSTT1 polymorphisms significantly affected comet parameters. Subjects bearing a GSTM1pos genotype showed a significantly higher proportion of damaged nuclei compared to people lacking GSTM1-1 expression (GSTM1null), whereas GSTT1pos workers showed significantly lower DNA damage than GSTT1null individuals. Styrene-7,8-oxide (SO)-induced DNA damage was assessed in vitro in WBCs isolated from the healthy controls. A clear dose-response relationship at micromolar doses of SO was found for the whole group. WBCs collected from subjects bearing the homozygous wildtype GSTP1 genotype showed a significant protection compared to cells from subjects bearing at least one GSTP1 variant allele. The field survey confirms that styrene exposure is associated with increased DNA damage and indicates a modulating role for GSTM1 and GSTT1 genotypes. In vitro experiments suggest that the extent of SO-induced DNA strand breaks depends, at least in part, on interindividual differences in GSH-conjugation capabilities.
[Show abstract] [Hide abstract]
ABSTRACT: Ab-initio molecular orbital calculations were carried out for a series of phosphazine compounds, (NPX2)n, X=H, F, Cl, and Br, n=2 through 6, in order to study the electronic structure of such compounds and explore their use as model compounds for the bulk polymer. Calculations were carried out at the Hartree–Fock level of theory, using all-electron triple-zeta plus polarization basis sets for all atoms. Full geometry optimizations followed by frequency calculations were performed. Although most species adopted hightly symmetric geometries they were often significantly nonplanar. Optimized geometries are general agreement with geometry's inferred from solution phase IR studies. The geometries of the eight membered and larger rings are very dependent on the identity of X. Ionization energies for this series were calculated using electron propagator theory. Good agreement with experimentally observed values is found. Phosphorus d basis functions appear to be serving as polarization functions rather than being formally involved in bonding.Polyhedron 01/2003; 22(3):473-482. · 2.05 Impact Factor
Antibiotiques 12/2010; 12(4):181-182. DOI:10.1016/j.antinf.2010.11.001
[Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to investigate the ability of epoxides of styrene (styrene-7,8-oxide; SO) and 1,3-butadiene (3,4-epoxy-1-butene; 1,2:3,4:-diepoxybutane) to cause oxidative stress and oxidative DNA damage on human peripheral blood mononuclear cells (PBMCs) and whether a complex mixture of olive oil phenols (OOPE) could prevent these effects. The DNA damage was measured by the single-cell gel electrophoresis (SCGE; comet assay). We found that the DNA damage induced by alkene epoxides could be prevented by N-acetyl-cysteine (10 mM) and catalase (100 U/ml). Alkene epoxides caused a significant (P < 0.05) increase of both peroxide concentration in extra- and intracellular environment and formamidopyrimidine DNA glycosylase (FPG)- and Endonuclease III (ENDO III)-sensitive sites in PBMCs, demonstrating the presence of oxidized bases. OOPE (1 μg of total phenols/ml) was able to prevent the alkene epoxide induced DNA damage both after 2 and 24 h of incubation. In addition, OOPE completely inhibited the SO-induced intracellular peroxide accumulation in PBMCs and prevented the oxidative DNA damage induced by SO, as evidenced by the disappearance of both FPG- and ENDO III-sensitive sites. This is the first study demonstrating the ability of OOPE to prevent the DNA damage induced by alkene epoxides providing additional information about the chemopreventive properties of olive oil.Nutrition and Cancer 10/2014; 66(8):1-9. DOI:10.1080/01635581.2014.956251 · 2.47 Impact Factor