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.
American Conference of Governmental Industrial Hygienists (ACGIH). 2003. TLVs and BEIs; Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices. Cincinnati: ACGIH. 206 p.
Anwar, Mutat Res, 327, 41 (1995)
Arand, Anal Biochem, 236, 184 (1996)
Artuso, Arch Environ Contam Toxicol, 29, 270 (1995)
Bastlova, Carcinogenesis, 16, 2357 (1995)
Bernardini, Carcinogenesis, 23, 893 (2002)
Bonassi, Mutat Res, 543, 155 (2003)
Brenneman, Mutat Res, 459, 89 (2000)
Brenner, Mutat Res, 261, 225 (1991)
Chakrabarti, Mutat Res, 395, 37 (1997)
Christakopoulos, Scand J Work Environ Health, 19, 255 (1993)
David-Beabes, Cancer Epidemiol Biomarkers Prev, 10, 911 (2001)
De Boeck, Environ Mol Mutagen, 36, 151 (2000a)
De Boeck, Carcinogenesis, 19, 2021 (1998)
De Boeck, Mutat Res, 469, 181 (2000b)
Dypbukt, Carcinogenesis, 13, 417 (1992)
Farmer, Toxicol Lett, 82-83, 757 (1995)
Fustinoni, Int Arch Occup Environ Health, 71, 35 (1998)
Goode, Cancer Epidemiol Biomarkers Prev, 11, 1513 (2002)
Haufroid, Clin Chem, 44, 2210 (1998)
Haufroid, Pharmacogenetics, 12, 691 (2002)
Haufroid, Int Arch Occup Environ Health, 71, 162 (1998)
IARC. 2002. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; some Traditional Herbal Medicines, some Mycotoxins, Naphthalene and Styrene. Lyon: IARC Press. 550 p.
Ikeda, Int Arch Occup Environ Health, 49, 325 (1982)
Kirsch-Volders, Mutagenesis, 16, 51 (2001)
Kogevinas, Scand J Work Environ Health, 20, 251 (1994)
Kolstad Henrik A, Lynge Elsebeth, Olsen Jørn, Breum N, Incidence of lymphohematopoietic malignancies among styrene-exposed workers of the reinforced plastics industry., 10.5271/sjweh.1398
Laffon, Toxicology, 171, 175 (2002)
Laffon, Mutat Res, 536, 49 (2003a)
Laffon, Toxicology, 186, 131 (2003b)
Lancaster, Mol Carcinog, 17, 160 (1996)
2001. Industrial Chemical Exposure; Guidelines for Biological Monitoring. Florida: CRC Press.
Leprat, Int J Radiat Oncol Biol Phys, 40, 10197 (1998)
Lu, Cell Biochem Biophys, 35, 141 (2001)
Lunn, Cancer Res, 59, 2557 (1999)
Maki-Paakkanen, Environ Mol Mutagen, 17, 27 (1991)
Manini, Rapid Commun Mass Spectrom, 14, 2055 (2000)
Marczynski, Med Hypotheses, 54, 619 (2000)
Mohrenweiser, Mutat Res, 526, 93 (2003)
Mutti, Toxicol Lett, 108, 77 (1999)
Norppa, Mutat Res, 544, 339 (2003)
Pagano, Environ Mutagen, 4, 575 (1982)
Pauwels, Mutat Res, 418, 21 (1998)
Pauwels, Carcinogenesis, 17, 2673 (1996)
Sarmanova, Pharmacogenetics, 10, 781 (2000)
Seiler, Mutat Res, 245, 165 (1990)
Severi, Scand J Work Environ Health, 20, 451 (1994)
Shield, Environ Mol Mutagen, 37, 285 (2001)
Shinmura, Antioxid Redox Signal, 3, 597 (2001)
Singh, Exp Cell Res, 175, 184 (1988)
Somorovská M, Jahnová E, Tulinská J, Zámečnı́ková M, Šarmanová J, Terenová A, Vodičková L, Lı́šková A, Vallová B, Souček P, Hemminki K, Norppa H, Hirvonen A, Tates A.D, Fuortes L, Dušinská M, Vodička P, Biomonitoring of occupational exposure to styrene in a plastics lamination plant, 10.1016/s1383-5742(99)00052-6
Sumner, Crit Rev Toxicol, 24, s11 (1994)
Touil, Mutagenesis, 17, 223 (2002)
Tsuda, Mutat Res, 467, 83 (2000)
Tuimala, Carcinogenesis, 23, 1003 (2002)
Van Hummelen, Mutat Res, 310, 157 (1994)
Vodicka, Carcinogenesis, 16, 1473 (1995)
Vodicka, Carcinogenesis, 25, 757 (2004)
Vodicka, Mutat Res, 482, 89 (2001)
Vodicka, Int Arch Occup Environ Health, 75, s75 (2002)
Vodicka, Mutat Res, 445, 205 (1999)
Vodicka, Carcinogenesis, 15, 1949 (1994)
Winsey, Cancer Res, 60, 5612 (2000)
Wood, Science, 291, 1284 (2001)
Bibliographic reference
Godderis, Lode ; De Boeck, Marlies ; Haufroid, Vincent ; Emmery, Muriel ; Mateuca, Raluca ; et. al. Influence of genetic polymorphisms on biomarkers of exposure and genotoxic effects in styrene-exposed workers.. In: Environmental and molecular mutagenesis, Vol. 44, no. 4, p. 293-303 (2004)