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.

Biomonitoring of Human Exposure to Prestige Oil: Effects on DNA and Endocrine Parameters

“…It is well known that GSTP1 enzyme takes part in the pulmonary detoxification of inhaled PAH and in oxidative stress processes (Buschini et al 2003). GSTP1 enzymes with Val105 have a seven-fold higher efficiency for PAH dihydrodiol-epoxides (Hu et al 1997) but this form is three-fold less effective using low size substrates as 1-chloro-2, 4-dimethylbenzene (Ali-Osman et al 1997).…”

Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile105Val polymorphism

“…This may explain why the geneenvironment association between GSTP1 Val 105 and occupational PAH exposures from petroleum sources were significant in our study while those from wood or coal were not. Interestingly, several studies have shown that GSTP1 variants are associated with an increase in biomarkers of DNA damage when subject to high PAH-exposure environments [48,49].…”

Metabolism and Toxicity of Styrene in Microsomal Epoxide Hydrolase-Deficient Mice

“…Teixeira et al (2007) showed that reinforced plastics workers exposed to styrene who had mEH genotypes with low activity had more styrene oxide-hemoglobin adducts than those with high activity. However, Buschini et al (2003) using the comet assay were not able to detect differences in DNA damage in styrene-exposed workers based on mEH genotypes.…”