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Evaluating chromosomal damage in workers exposed to hexavalent chromium and the modulating role of polymorphisms of DNA repair genes

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Abstract

Purpose

Welders have been chronically exposed to hexavalent chromium with potential consequences on chromosomal integrity. Our study is focused on the extent of any such chromosomal aberrations with respect to chromium levels in the blood of welders as well as on the tentative modulating role of polymorphisms in DNA repair genes XPD Lys751Gln, XPG Asn114His, XPC Lys939Gln, hOGG1 Ser326Cys and XRCC1 Arg399Gln on chromosomal damage.

Methods

The study was conducted on 144 individuals consisting of 73 welders exposed to chromium for 10.2 ± 1.67 years and 71 control individuals without known exposures. Chromosomal aberrations, their chromatid-type and chromosome-type aberrations were detected by conventional cytogenetic analysis. XPD, XPG, XPC, hOGG1 and XRCC1 gene polymorphisms were assayed for by Taqman SNP genotyping assay (“Assay-by-Demand”) using Real-Time allelic discrimination on AB 7500 equipment. Chromium concentration in the blood was determined by atomic absorption spectrophotometry.

Results

The level of chromium in the blood of welders ranged between 0.032 and 0.182 μmol l−1 and was significantly higher than that in controls (0.07 ± 0.04 μmol l−1 vs. 0.03 ± 0.007 μmol l−1). Parameters of chromosomal damage were similar in both the exposed and the control individuals (1.89% vs. 1.70% for total chromosomal aberrations, 0.97% vs. 0.88% for chromosome-type and 0.92% vs. 0.80% for chromatid-type, respectively). Chromatid-type of aberrations positively correlated with the level of chromium in the blood (r = 0.28; P = 0.02). Significantly higher total chromosomal aberrations were detected in individuals with homozygous variant polymorphism in XRCC1 Arg399Gln gene as compared to those with heterozygous and homozygous wild-type genotypes (2.20, 1.89 and 1.48%, respectively; P = 0.01). A similar tendency was found for chromatid-type aberrations (1.30% for homozygous variant genotype bearers, 0.94% for those with heterozygous genotype and 0.75% for carriers of homozygous wild-type genotype, respectively; P = 0.04).

Conclusions

Although no apparent increase in chromosomal damage was recorded in chromium-exposed welders in comparison with controls, genetic make-up in DNA repair genes may increase susceptibility toward adverse effect of chromium.

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References

  • Abrahim KS, Abdet-Gawad NB, Mahmoud AM, El-Gowaily MM, Emara AM, Hwaihy MM (2011) Genotoxic effect of occupational exposure to cadmium. Toxicol Ind Health 27:173–179

    Article  CAS  Google Scholar 

  • Albertini R, Clewell H, Himmelstein MW, Morinello E, Olin S, Preston J, Scarano L, Smith MT, Swenberg J, Tice R, Travis C (2003) The use of non-tumor data cancer risk assessment reflections on butadiene, vinyl chloride, and benzene. Regul Toxicol Pharm 37:105–132

    Article  CAS  Google Scholar 

  • Angelini S, Kumar R, Carbone F, Maffei F, Forti GC, Violante FS, Lodi V, Curti S, Hemminki K, Hrelia P (2005) Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes. Mutat Res 570:105–117

    Article  CAS  Google Scholar 

  • Angelini S, Kumar R, Bermejo JL, Maffei F, Barbieri A, Graziosi F, Carbone F, Cantelli-Forti G, Violante FS, Hemminki K, Hrelia P (2011) Exposure to low environmental levels of benzene: evaluation of micronucleus frequencies and S-phenylmercapturic acid excretion in relation to polymorphisms in genes encoding metabolic enzymes. Mutat Res 719:7–13

    CAS  Google Scholar 

  • Au WW, Salama SA (2006) Cytogenetic challenge assays for assessment of DNA repair capacities. Methods Mol Biol 314:25–42

    Article  CAS  Google Scholar 

  • Balachandar V, Arun M, Mohana Devi S, Velmurugan P, Manikantan P, Karthick Kumar A, Sasikala K, Venkatesan C (2010) Evaluation of the genetic alterations in direct and indirect exposures of hexavalent chromium [Cr(VI)] in leather tanning industry workers North Arcot District, South India. Int Arch Occup Environ Health 83:791–801

    Article  CAS  Google Scholar 

  • Berwick M, Vineis P (2000) Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 92:874–897

    Article  CAS  Google Scholar 

  • Beveridge R, Pintos J, Parent ME, Asselin J, Siemiatycki J (2010) Lung cancer risk associated with occupational exposure to nickel, chromium VI, and cadmium in two population-based case–control studies in Montreal. Am J Ind Med 53:476–485

    Google Scholar 

  • Brand P, Gube M, Gerards K, Bertram J, Kaminski H, John AC, Kuhlbusch T, Wiemann M, Eisenbeis C, Winkler R, Kraus T (2010) Internal exposure, effect monitoring, and lung function in welders after acute short-term exposure to welding fumes from different welding processes. J Occup Environ Med 52:887–892

    Article  CAS  Google Scholar 

  • Bryant PE, Riches AC, Terry SY (2010) Mechanisms of the formation of radiation-induced chromosomal aberrations. Mutat Res 701:23–26

    CAS  Google Scholar 

  • Chen J, Suter B (2003) XPD a structural bridge and a functional link. Cell Cycle 2:503–506

    Article  CAS  Google Scholar 

  • Christmann M, Tomicic MT, Roos WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193:3–34

    Article  CAS  Google Scholar 

  • Crespo-López ME, Macêdo GL, Arrifano GP, Pinheiro Mda C, do Nascimento JL, Herculano AM (2011) Genotoxicity of mercury: contributing for the analysis of Amazonian populations. Environ Int 37:136–141

    Article  Google Scholar 

  • Dai H, Liu J, Malkas LH, Catalano J, Alagharu S, Hickey RJ (2009) Chromium reduces the in vitro activity and fidelity of DNA replication mediated by the human cell DNA synthesome. Toxicol Appl Pharmacol 236:154–165

    Article  CAS  Google Scholar 

  • Figgitt M, Newson R, Leslie IJ, Fisher J, Ingham E, Case CP (2010) The genotoxicity of physiological concentrations of chromium (Cr(III) and Cr(VI)) and cobalt (Co(II)): an in vitro study. Mutat Res 688:53–61

    Article  CAS  Google Scholar 

  • Franco SS, Nardocci AC, Günther WM (2008) PAH biomarkers for human health risk assessment: a review of the state-of-the-art. Cad Saude Publica Suppl 4:569–580

    Google Scholar 

  • Friedberg EC (2001) How nucleotide excision repair protects against cancer. Nat Rev Cancer 1:22–33

    Article  CAS  Google Scholar 

  • García-Lestón J, Méndez J, Pásaro E, Laffon B (2010) Genotoxic effects of lead: an updated review. Environ Int 36:623–636

    Article  Google Scholar 

  • Ghosh M, Bandyopadhyay M, Mukherjee A (2010) Genotoxicity of titanium dioxide (TiO2) nanoparticles at two trophic levels: plant and human lymphocytes. Chemosphere 81:1253–1262

    Article  CAS  Google Scholar 

  • Grlickova-Duzevik E, Wise SS, Munroe RC, Thompson WD, Wise JP Sr (2006) XRCC1 protects against particulate chromate–induced chromosome damage and cytotoxicity in Chinese hamster ovary cells. Toxicol Sci 92:96–102

    Article  CAS  Google Scholar 

  • Halasova E, Bukovska E, Kukura F, Cervenova T, Oravec P, Kereskeni J (2001) Do works concerning ferrochromium alloys mean risk for inhabitants living in their surrounding? A cytogenetic study. Biologia 56:679–683

    Google Scholar 

  • Halasova E, Baska T, Kukura F, Mazurova D, Bukovska E, Dobrota D, Poliacek I, Halasa M (2005) Lung cancer in relation to occupational and environmental chromium exposure and smoking. Neoplasma 52:287–291

    CAS  Google Scholar 

  • Hanawalt PC (2002) Subpathways of nucleotide excision repair and their regulation. Oncogene 21:8949–8956

    Article  CAS  Google Scholar 

  • Hashiguchi K, Stuart JA, de Souza-Pinto NC, Bohr VA (2004) The C-terminal alphaO helix of human Ogg1 is essential for 8-oxoguanine DNA glycosylase activity: the mitochondrial beta-Ogg1 lacks this domain and does not have glycosylase activity. Nucleic Acids Res 32:5596–5608

    Article  CAS  Google Scholar 

  • Haveric A, Haveric S, Ibrulj S (2010) Micronuclei frequencies in peripheral blood and buccal exfoliated cells of young smokers and non-smokers. Toxicol Mech Methods 20:260–266

    Article  CAS  Google Scholar 

  • Hodges NJ, Chipman JK (2002) Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells. Carcinogenesis 23:55–60

    Article  CAS  Google Scholar 

  • Hopf NB, Kirkeleit J, Kramer SL, Moen B, Succop P, Genter MB, Carreon T, Mack J, Talaska G (2010) Urinary 1-hydroxypyrene levels in offshore workers. Int Arch Occup Environ Health 83:55–59

    Article  CAS  Google Scholar 

  • Hu YC, Ahrendt SA (2005) hOGG1 Ser326Cys polymorphism and G:C-to-T:A mutations: no evidence for a role in tobacco-related non small cell lung cancer. Int J Cancer 114:387–393

    Article  CAS  Google Scholar 

  • IARC (International Agency for Research on Cancer) (1990) IARC monographs on the evaluation of carcinogenic risks to humans, vol 49: chromium nickel and welding. Lyon, France, pp 249–256

  • Iarmarcovai G, Sari-Minodier I, Chaspoul F, Botta C, De Meo M, Orsiere T, Berge-Lefranc JL, Gallice P, Botta A (2005) Risk assessment of welders using analysis of eight metals by ICP-MS in blood and urine and DNA damage evaluation by the comet and micronucleus assays; influence of XRCC1and XRCC3 polymorphisms. Mutagenesis 20:425–432

    Article  CAS  Google Scholar 

  • Jakusova V, Murajda L, Poliacek I, Jakus J (2010) Risk of ultraviolet radiation—health protection of university student. Acta Med Mart 7:26–30

    Google Scholar 

  • Kiuru A, Lindholm C, Heilimo I, Ceppi M, Koivistoinen A, Ilus T, Hirvonen A, Norppa H, Salomaa S (2005) Influence of DNA repair gene polymorphisms on the yield of chromosomal aberrations. Environ Mol Mutagen 46:198–205

    Article  CAS  Google Scholar 

  • Kohno T, Kunitoh H, Toyama K, Yamamoto S, Kuchiba A, Saito D, Yanagitani N, Ishihara S, Saito R, Yokota J (2006) Association of the OGG1-Ser326Cys polymorphism with lung adenocarcinoma risk. Cancer Sci 97:724–728

    Article  CAS  Google Scholar 

  • Kubrak OI, Lushchak OV, Lushchak JV, Torous IM, Storey JM, Storey KB, Lushchak VI (2010) Chromium effects on free radical processes in goldfish tissues: Comparison of Cr(III) and Cr(VI) exposures on oxidative stress markers, glutathione status and antioxidant enzymes. Comp Biochem Physiol C Toxicol Pharmacol 152:360–370

    Article  Google Scholar 

  • Ladeira C, Viegas S, Carolino E, Prista J, Gomes MC, Brito M (2011) Genotoxicity biomarkers in occupational exposure to formaldehyde-the case of histopathology laboratories. Mutat Res 721:15–20

    CAS  Google Scholar 

  • Lee AJ, Hodges NJ, Chipman JK (2005) Interindividual variability in response to sodium dichromate-induced oxidative DNA damage: role of the Ser326Cys polymorphism in the DNA-repair protein of 8-oxo-7,8-dihydro-2′-deoxyguanosine DNA glycosylase 1. Cancer Epidemiol Biomarkers Prev 14:497–505

    Article  CAS  Google Scholar 

  • Leonard SS, Roberts JR, Antonini JM, Castranova V, Shi X (2004) PBCrO4 mediates cellular responses via reactive oxygen species. Mol Cell Biochem 255:171–179

    Article  CAS  Google Scholar 

  • Mambo E, Chatterjee A, de Souza-Pinto NC, Mayard S, Hogue BA, Hoque MO, Dizdaroglu M, Bohr VA, Sidransky D (2005) Oxidized guanine lesions and hOgg1 activity in lung cancer. Oncogene 24:4496–4508

    Article  CAS  Google Scholar 

  • Meeker JD, Susi P, Flynn MR (2010) Hexavalent chromium exposure and control in welding tasks. J Occup Environ Hyg 11:607–615

    Article  Google Scholar 

  • Miller BG, Fransman W, Heederik D, Hurley JF, Kromhout H, Fitzsimons E (2010) A review of the data quality and comparability of case–control studies of low-level exposure to benzene in the petroleum industry. Int Arch Occup Environ Health 83:69–76

    Article  CAS  Google Scholar 

  • Møller P, Knudsen LE, Loft S, Wallin H (2000) The comet assay as a rapid test in biomonitoring occupational exposure to DNA-damaging agents and effect of confounding factors. Cancer Epidemiol Biomarkers Prev 9:1005–1015

    Google Scholar 

  • Musak L, Vodicka P, Klimentova G, Soucek P, Hanova M, Mikulkova R, Buchancova J, Vodickova L, Polakova V, Pec M (2006) Chromosomal damage and polymorphisms of DNA repair genes XRCC1 and XRCC3 in workers exposed to cytostatics. Neuro Endocrinol Lett 27(Suppl 2):57–60

    CAS  Google Scholar 

  • Musak L, Soucek P, Vodickova L, Naccarati A, Halasova E, Polakova V, Slyskova J, Susova S, Buchancova J, Smerhovsky Z, Sedikova J, Klimentova G, Osina O, Hemminki K, Vodicka P (2008) Chromosomal aberrations in tire plant workers and interaction with polymorphisms of biotransformation and DNA repair genes. Mut Res 641:36–42

    Article  CAS  Google Scholar 

  • Natarajan AT, Obe G (1980) Screening of human populations for mutations induced by environmental pollutants: use of human lymphocyte system. Ecotoxicol Environ Saf 4:468–481

    Article  CAS  Google Scholar 

  • Pantelias GE, Terzoudi GI (2010) Functional cell-cycle chromatin conformation changes in the presence of DNA damage result into chromatid breaks: a new insight in the formation of radiation-induced chromosomal aberrations based on the direct observation of interphase chromatin. Mutat Res 701:27–37

    CAS  Google Scholar 

  • Pavanello S, Bollati V, Pesatori AC, Kapka L, Bolognesi C, Bertazzi PA, Baccarelli A (2009) Global and gene-specific promoter methylation changes are related to anti-B[a] PDE-DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon-exposed individuals. Int J Cancer 125:1692–1697

    Article  CAS  Google Scholar 

  • Pavanello S, Pesatori AC, Dioni L, Hoxha M, Bollati V, Siwinska E, Mielzyńska D, Bolognesi C, Bertazzi PA, Baccarelli A (2010) Shorter telomere length in peripheral blood lymphocytes of workers exposed to polycyclic aromatic hydrocarbons. Carcinogenesis 31:216–221

    Article  CAS  Google Scholar 

  • Polakova V, Pardini B, Naccarati A, Landi S, Slyskova J, Novotny J, Vodickova L, Bermejo JL, Hanova M, Smerhovsky Z, Tulupova E, Kumar R, Hemminki K, Vodicka P (2009) Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. Hum Mutat 30:661–668

    Article  CAS  Google Scholar 

  • Qu T, Morii E, Oboki K, Lu Y, Morimoto K (2005) Micronuclei in EM9 cells expressing polymorphic forms of human XRCC1. Cancer Lett 221:91–95

    Article  CAS  Google Scholar 

  • Quievryn G, Messer J, Zhitkovich A (2002) Carcinogenic chromium (VI) induces cross-linking of vitamin C to DNA in vitro and in human lungs A549 cells. Biochemistry 41:3156–3167

    Article  CAS  Google Scholar 

  • Rodrigues CF, Urbano AM, Matoso E, Carreira I, Almeida A, Santos P, Botelho F, Carvalho L, Alves M, Monteiro C, Costa AN, Moreno V, Alpoim MC (2009) Human bronchial epithelial cells malignantly transformed by hexavalent chromium exhibit an aneuploid phenotype but no microsatellite instability. Mutat Res 670:42–52

    Article  CAS  Google Scholar 

  • Rondelli CM, El-Zein RA, Wickliffe JK, Etzel CJ, Abdel-Rahman SZ (2010) A comprehensive haplotype analysis of the XPC genomic sequence reveals a cluster of genetic variants associated with sensitivity to tobacco-smoke mutagens. Toxicol Sci 115:41–50

    Article  CAS  Google Scholar 

  • Rossi AM, Hansteen IL, Skjelbred CF, Ballardin M, Maggini V, Murgia E, Tomei A, Viarengo P, Knudsen LE, Barale R, Norppa H, Bonnassi S (2009) Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1. Environ Health Perspect 117:203–208

    CAS  Google Scholar 

  • Rzeszowska-Wolny J, Polanska J, Pietrowska M, Palyvoda O, Jaworska J, Butkiewicz D, Hancock R (2005) Influence of polymorphisms in DNA repair genes XPD, XRCC1 and MGMT on DNA damage induced by gamma radiation and its repair in lymphocytes in vitro. Radiat Res 164:132–140

    Article  CAS  Google Scholar 

  • Singh S, Kumar V, Thakur S, Banerjee BD, Rautela RS, Grover SS, Rawat DS, Pasha ST, Jain SK, Ichhpujani RL, Rai A (2011) Paraoxonase-1 genetic polymorphisms and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides. Toxicol Appl Pharmacol 252:130–137

    Article  CAS  Google Scholar 

  • Skjelbred CF, Svendsen M, Haugan V, Eek AK, Clausen KO, Svendsen MV, Hansteen IL (2006) Influence of DNA repair gene polymorphisms of hOGG1, XRCC1, XRCC3, ERCC2 and the folate metabolism gene MTHFR on chromosomal aberration frequencies. Mutat Res 602:151–162

    Article  CAS  Google Scholar 

  • Skjelbred CF, Svendsen M, Haugan V, Eek AK, Clausen KO, Kure EH, Tuimala JT, Svendsen MV, Norpa H (2011) Influence of GSTM1, GSTT1, GSTP1, NAT 1, NAT2, EXPHX1, and MTHFR polymorphism on chromosomal aberration frequencies in human lymphocytes. Carcinogenesis 32:399–405

    Article  CAS  Google Scholar 

  • Srivastava RK, Lohani M, Pant AB, Rahman Q (2010) Cyto-genotoxicity of amphibole asbestos fibers in cultured human lung epithelial cell line: role of surface iron. Toxicol Ind Health 26:575–582

    Article  CAS  Google Scholar 

  • Sun P, Qian J, Zhang ZB, Wan JX, Wu F, Jin XP, Fan WW, Lu DR, Zhao NQ, Christiani DC, Xia ZL (2008) Polymorphisms in phase I and phase II metabolism genes and risk of chronic benzene poisoning in a Chinese occupational population. Carcinogenesis 29:2325–2329

    Article  CAS  Google Scholar 

  • Tajima H, Yoshida T, Ohnuma A, Fukuyama T, Hayashi K, Yamaguchi S, Ohtsuka R, Sasaki J, Tomita M, Kojima S, Takahashi N, Kashimoto Y, Kuwahara M, Takeda M, Kosaka T, Nakashima N, Harada T (2010) Pulmonary injury and antioxidant response in mice exposed to arsenate and hexavalent chromium and their combination. Toxicology 267:118–124

    Article  CAS  Google Scholar 

  • Tsaousi A, Jones E, Case CP (2010) The in vitro genotoxicity of orthopaedic ceramic (Al2O3) and metal (CoCr alloy) particles. Mut Res 697:1–9

    CAS  Google Scholar 

  • Velma V, Tchounwou PB (2010) Chromium-induced biochemical, genotoxic and histopathologic effects in liver and kidney of goldfish, carassius auratus. Mut Res 698:43–51

    CAS  Google Scholar 

  • Vidal AE, Boiteux S, Hickson ID, Radicella P (2001) XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein–protein interactions. EMBO J 20:6530–6539

    Article  CAS  Google Scholar 

  • Vodicka P, Stetina R, Polakova V, Tulupova E, Naccarati A, Vodickova L, Kumar R, Hanova M, Pardini B, Slyskova J, Musak L, De Palma G, Soucek P, Hemminki K (2007) Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects. Carcinogenesis 28:657–664

    Article  CAS  Google Scholar 

  • Vodicka P, Polivkova Z, Sytarova S, Demova H, Kucerova M, Vodickova L, Polakova V, Naccarati A, Smerhovsky Z, Ambrus M, Cerna M, Hemminki K (2010) Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls. Carcinogenesis 1:1238–1241

    Article  Google Scholar 

  • Wood RD, Mitchell M, Sgouros J, Lindahl T (2001) Human DNA repair genes. Science 291:1284–1289

    Article  CAS  Google Scholar 

  • Wu F, Zhang Z, Wan J, Gu S, Liu W, Jin X, Xia Z (2008) Genetic polymorphisms in hMTH1, hOGG1 and hMYH and risk of chronic benzene poisoning in a Chinese occupational population. Toxicol Appl Pharmacol 233:447–453

    Article  CAS  Google Scholar 

  • Yamane A, Kohno T, Ito K, Sunaga N, Aoki K, Yoshimura K, Murakami H, Nojima Y, Yokota J (2004) Differential ability of polymorphic OGG1 proteins to suppress mutagenesis induced by 8-hydroxyguanine in human cell in vivo. Carcinogenesis 25:1689–1694

    Article  CAS  Google Scholar 

  • Zafereo ME, Sturgis EM, Liu Z, Wang LE, Wei Q, Li G (2009) Nucleotide excision repair core gene polymorphisms and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck. Carcinogenesis 30:997–1002

    Article  CAS  Google Scholar 

  • Zhang JY, Wang Y, Prakash C (2006) Xenobiotic-metabolizing enzymes in human lung. Curr Drug Metab 8:939–948

    Article  Google Scholar 

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Acknowledgments

This work was supported by the grant of the Ministry of Health of the Slovak Republic No. 2007-UK48/13 and by the grant of the Ministry of Education of the Slovak Republic No. 1/0537/10.

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The authors declare that they have no conflict of interest.

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Halasova, E., Matakova, T., Musak, L. et al. Evaluating chromosomal damage in workers exposed to hexavalent chromium and the modulating role of polymorphisms of DNA repair genes. Int Arch Occup Environ Health 85, 473–481 (2012). https://doi.org/10.1007/s00420-011-0684-x

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