Influence of genetic polymorphisms on biomarkers of exposure and genotoxic effects in styrene-exposed workers.
A study on 44 workers exposed to styrene and 44 matched referents was performed in order to examine the influence of genetic polymorphisms in biotransformation and DNA repair enzymes on the levels of N-terminal hemoglobin adducts and genotoxicity biomarkers. Urinary mandelic acid concentration averaged 201.57 mg/g creatinine +/-148.32 in exposed workers, corresponding to a calculated average airborne styrene exposure of 9.5 ppm +/-9.6. Individuals with a high level of N-terminal valine adducts had higher levels of DNA damage, as evaluated by the Comet assay (r = 0.29, P = 0.008). Frequencies of micronucleated mononucleated lymphocytes (MNMC) (0.71 +/- 0.88 vs 0.11 +/- 0.20, P<0.0001), micronucleated binucleated lymphocytes (MNBC) (3.93 +/- 2.75 vs 2.65 +/- 1.94, p = 0.02) and micronucleated nasal epithelial cells (0.52 +/- 0.49 vs 0.23 +/- 0.31, p = 0.04) differed significantly between the exposed and referent groups. In the whole group of 88 individuals, higher frequencies of MNMC were found in individuals possessing the XRCC3 Met(241) allele and those individuals with the XRCC1 Gln( (399) ) allele showed higher frequencies of MNMC and MNCB. In vitro DNA repair capacity, as measured by residual DNA strand breaks in peripheral blood leukocytes after a styrene oxide challenge, was also influenced by styrene exposure, with an apparent induction of early repair mechanisms associated with the intensity of recent exposure and a reduction of late (24 h) repair capacity that was associated with the duration of employment. After 1 h of repair, lower levels of residual DNA damage were found in individuals possessing GSTT1 (P = 0.043). After 24 h of repair, lower residual DNA damage was found in individuals homozygous for XRCC1 Arg(194) (P = 0.013). Multivariate regression analysis indicated that the duration of exposure, smoking habits and polymorphisms of XRCC1 at codon 399 were important variables affecting the genotoxic responses. Our data suggest that DNA damage is formed in workers exposed to low concentrations of styrene, and that genotypes of metabolising and DNA-repair genes are important for the assessment of individual genotoxic risk to styrene. The in vitro DNA repair phenotype assay might be a valuable method to estimate the susceptibility of workers.
Katholieke Universiteit Leuven, Laboratorium voor Arbeidshygiëne en-Toxicologie, 3000 Leuven, Belgium.
Lode
L
Godderis
Marlies
M
De Boeck
Vincent
V
Haufroid
Muriel
M
Emmery
Raluca
R
Mateuca
Sophie
S
Gardinal
Micheline
M
Kirsch-Volders
Hendrik
H
Veulemans
Dominique
D
Lison
D000328:Adult; D001530:Belgium; D015415:Biomarkers / Q000378:metabolism; D020552:Comet Assay; D018736:DNA Adducts / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004798:Enzymes / Q000235:genetics*; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008333:Mandelic Acids / Q000652:urine; D015162:Micronucleus Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D020058:Styrene / Q000633:toxicity*; D014633:Valine / Q000235:genetics
D015415:Biomarkers; D018736:DNA Adducts; D004798:Enzymes; D006454:Hemoglobins; D008333:Mandelic Acids; D020058:Styrene; D045643:DNA Repair Enzymes; D014633:Valine; C037938:mandelic acid