Association between genetic polymorphisms and biomarkers in styrene-exposed workers
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
11535253
DOI
10.1016/s0027-5107(01)00214-7
PII: S0027510701002147
Knihovny.cz E-resources
- MeSH
- Biomarkers MeSH
- Chromosome Aberrations MeSH
- Cytochrome P-450 CYP1A1 genetics MeSH
- Cytochrome P-450 CYP2E1 genetics MeSH
- Adult MeSH
- Enzymes genetics metabolism MeSH
- Epoxide Hydrolases genetics MeSH
- Glutathione S-Transferase pi MeSH
- Glutathione Transferase genetics MeSH
- Hypoxanthine Phosphoribosyltransferase drug effects genetics MeSH
- Isoenzymes genetics MeSH
- DNA, Single-Stranded drug effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Inactivation, Metabolic MeSH
- Mutation MeSH
- Mutagens adverse effects MeSH
- Polymorphism, Genetic * MeSH
- DNA Damage drug effects genetics MeSH
- Occupational Exposure * MeSH
- Case-Control Studies MeSH
- Styrene adverse effects metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
- Cytochrome P-450 CYP1A1 MeSH
- Cytochrome P-450 CYP2E1 MeSH
- Enzymes MeSH
- Epoxide Hydrolases MeSH
- Glutathione S-Transferase pi MeSH
- glutathione S-transferase M1 MeSH Browser
- glutathione S-transferase T1 MeSH Browser
- Glutathione Transferase MeSH
- GSTP1 protein, human MeSH Browser
- Hypoxanthine Phosphoribosyltransferase MeSH
- Isoenzymes MeSH
- DNA, Single-Stranded MeSH
- Mutagens MeSH
- Styrene MeSH
A comprehensive approach to evaluate genotoxic effects induced by styrene exposure was employed in 44 hand-lamination workers in comparison with 18 unexposed controls. The acquired data on single-strand breaks in DNA (SSBs), frequency of chromosomal aberrations and HPRT mutant frequency in peripheral blood lymphocytes were compared to the results on genotyping of some of the xenobiotic-metabolising enzymes (CYP1A1, CYP2E1, epoxide hydrolase and GSTM1, GSTP1 and GSTT1). Multifactorial regression analysis indicated that SSB in DNA were significantly associated with styrene exposure and with heterozygosity in CYP2E1 (5'-flanking region and intron 6; r(2)=0.614). The frequency of chromosomal aberrations (CA), as analysed by linear multiple regression analysis, significantly correlated with years of employment (P=0.004) and with combinations of epoxide hydrolase (EPHX) genotypes (exon 3, Tyr/His and exon 4, His/Arg), where individuals with low and medium activity EPHX genotypes exhibited higher frequencies of CA than those with high activity genotypes (P=0.044, r(2)=0.563). Moderately higher HPRT mutant frequencies were detected in styrene-exposed individuals (20.2 +/- 25.8 x 10(-6)) as compared to controls (13.3 +/- 6.3 x 10(-6)), but this difference was not significant. ANOVA (in the whole set of data) revealed that mutant frequencies at the HPRT gene were significantly associated with years of employment (F=6.9, P=0.0001), styrene in blood (F=10.1, P=0.0001), and heterozygosity in CYP2E1 (intron 6; F=13.5, P=0.0008) and GSTP1 (exon 5; F=3.6, P=0.038). In conclusion, our present data suggest that analysed biomarkers of DNA damage may be modulated by polymorphic CYP2E1, EPHX and GSTP1. In our study, styrene-specific DNA and haemoglobin adducts are under investigation. Completing these data with the results of genotyping of metabolising enzymes may provide a useful tool for individual genotoxic risk assessment.
References provided by Crossref.org
