Association between genetic polymorphisms and biomarkers in styrene-exposed workers
Jazyk angličtina Země Nizozemsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
11535253
DOI
10.1016/s0027-5107(01)00214-7
PII: S0027510701002147
Knihovny.cz E-zdroje
- MeSH
- biologické markery MeSH
- chromozomální aberace MeSH
- cytochrom P-450 CYP1A1 genetika MeSH
- cytochrom P-450 CYP2E1 genetika MeSH
- dospělí MeSH
- enzymy genetika metabolismus MeSH
- epoxid hydrolasy genetika MeSH
- glutathion-S-transferasa fí MeSH
- glutathiontransferasa genetika MeSH
- hypoxanthinfosforibosyltransferasa účinky léků genetika MeSH
- izoenzymy genetika MeSH
- jednovláknová DNA účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolická inaktivace MeSH
- mutace MeSH
- mutageny škodlivé účinky MeSH
- polymorfismus genetický * MeSH
- poškození DNA účinky léků genetika MeSH
- pracovní expozice * MeSH
- studie případů a kontrol MeSH
- styren škodlivé účinky metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- cytochrom P-450 CYP1A1 MeSH
- cytochrom P-450 CYP2E1 MeSH
- enzymy MeSH
- epoxid hydrolasy MeSH
- glutathion-S-transferasa fí MeSH
- glutathione S-transferase M1 MeSH Prohlížeč
- glutathione S-transferase T1 MeSH Prohlížeč
- glutathiontransferasa MeSH
- GSTP1 protein, human MeSH Prohlížeč
- hypoxanthinfosforibosyltransferasa MeSH
- izoenzymy MeSH
- jednovláknová DNA MeSH
- mutageny MeSH
- styren 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.
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