title: 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.
authors.affiliation: Department of Genetics, Anthropology, Evolution, University of Parma, Parma, Italy. annamaria.buschini@unipr.it
authors.forename: Annamaria
authors.initials: A
authors.lastname: Buschini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
authors.forename: Paola
authors.initials: P
authors.lastname: Poli
authors.forename: Anna
authors.initials: A
authors.lastname: Martino
authors.forename: Carlo
authors.initials: C
authors.lastname: Rossi
authors.forename: Paola
authors.initials: P
authors.lastname: Mozzoni
authors.forename: Eleonora
authors.initials: E
authors.lastname: Scotti
authors.forename: Luca
authors.initials: L
authors.lastname: Buzio
authors.forename: Enrico
authors.initials: E
authors.lastname: Bergamaschi
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
mesh_terms: D000328:Adult; D015331:Cohort Studies; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020058:Styrene / Q000633:toxicity*
chemical_list: D020058:Styrene; D005982:Glutathione Transferase