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

Halašová, Erika; Matáková, Tatiana; Musak, Ludovit; Polakova, Veronika; Letkova, Lucia; Dobrota, Dušan; Vodička, Pavel

doi:10.1007/s00420-011-0684-x

Cited by 25 publications

(9 citation statements)

References 64 publications

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“…CAs in PBL have been employed as biomarkers reflecting individual sensitivity to exogenous and endogenous genotoxic substances for many years (4,5). There are several reports pointing to the occupational exposure as a causative of enhanced CA frequencies for small molecular chemicals in plastics industry (32,43,44), for anaesthetic gases and antineoplastic drugs (9), for heavy metals (45) and for mineral fibres (6,7,38). In the present study, individuals that were occupationally exposed mainly to small molecular organic chemicals, anaesthetic gases, heavy metals and fibres (1207 subjects) indeed exhibited higher CAs, CTAs and CSAs in comparison with 989 unexposed individuals.…”

Section: Discussionmentioning

confidence: 99%

Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects

Vodička

Musak

Christoph

et al. 2015

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Human cancers are often associated with numerical and structural chromosomal instability. Structural chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL) arise as consequences of direct DNA damage or due to replication on a damaged DNA template. In both cases, DNA repair is critical and inter-individual differences in its capacity are probably due to corresponding genetic variations. We investigated functional variants in DNA repair genes (base and nucleotide excision repair, double-strand break repair) in relation to CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) in healthy individuals. Chromosomal damage was determined by conventional cytogenetic analysis. The genotyping was performed by both restriction fragment length polymorphism and TaqMan allelic discrimination assays. Multivariate logistic regression was applied for testing individual factors on CAs, CTAs and CSAs. Pair-wise genotype interactions of 11 genes were constructed for all possible pairs of single-nucleotide polymorphisms. Analysed individually, we observed significantly lower CTA frequencies in association with XPD Lys751Gln homozygous variant genotype [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.48-0.85, P = 0.004; n = 1777]. A significant association of heterozygous variant genotype in RAD54L with increased CSA frequency (OR 1.96, 95% CI 1.01-4.02, P = 0.03) was determined in 282 subjects with available genotype. By addressing gene-gene interactions, we discovered 14 interactions significantly modulating CAs, 9 CTAs and 12 CSAs frequencies. Highly significant interactions included always pairs from two different pathways. Although individual variants in genes encoding DNA repair proteins modulate CAs only modestly, several gene-gene interactions in DNA repair genes evinced either enhanced or decreased CA frequencies suggesting that CAs accumulation requires complex interplay between different DNA repair pathways.

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Section: Discussionmentioning

confidence: 99%

Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects

Vodička

Musak

Christoph

et al. 2015

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“…In another study, chromosomal aberrations were measured in welders exposed to chromium and in a control population. Significantly increased numbers of aberrations in lymphocytes were detected in individuals homozygous for the Arg399Gln variant [325] and correlated with levels of chromium in blood. In a third study, smokers carrying both alleles of the XRCC1 Arg399Gln variant had significantly increased frequencies of micronuclei and chromosomal aberrations [326].…”

Section: X-ray Cross Complementing 1 (Xrcc1)mentioning

confidence: 99%

Base excision repair and cancer

2012

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Base excision repair is the system used from bacteria to man to remove the tens of thousands of endogenous DNA damages produced daily in each human cell. Base excision repair is required for normal mammalian development and defects have been associated with neurological disorders and cancer. In this paper we provide an overview of short patch base excision repair in humans and summarize current knowledge of defects in base excision repair in mouse models and functional studies on short patch base excision repair germ line polymorphisms and their relationship to cancer. The biallelic germ line mutations that result in MUTYH-associated colon cancer are also discussed.

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“…A quantitative exposure assessment has been addressed as pivotal in occupational epidemiology (Ward et al 2010 ). Although millions of workers worldwide are exposed to welding fumes, only few and rather small studies measured respirable particles in the breathing zone of welders and explored their association with oxidatively damaged molecules together with pertinent covariates (Antonini 2003 ; Halasova et al 2012 ). Here, we applied statistical modeling to estimate the impact of airborne and systemic exposure to metals on the occurrence of oxidatively modified guanosine in urine and blood samples from welders.…”

Section: Introductionmentioning

confidence: 99%

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores

et al. 2014

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The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxidatively damaged guanosine in DNA of white blood cells (WBC) and in postshift urine samples from 238 welders. Medians of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) were 2.35/106 dGuo in DNA of WBC and 4.33 µg/g creatinine in urine. The median of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 7.03 µg/g creatinine in urine. The extent of both urinary parameters was higher in welders applying techniques with high particle emission rates to stainless steel than in tungsten inert gas welders (8-oxodGuo: 9.96 vs. 4.49 µg/L, 8-oxoGuo: 15.7 vs. 7.7 µg/L), but this apparent difference diminished after creatinine adjustment. We applied random intercept models to estimate the influence of airborne and systemic exposure to metals on oxidatively damaged guanosine in WBC and urine together with covariates. We observed a highly significant nonlinear association of urinary 8-oxoGuo with serum ferritin (P < 0.0001) and higher 8-oxoGuo concentrations for respirable iron >1,000 µg/m3 compared to ≤57 µg/m3. Similar effects were found for manganese. Airborne chromium but not nickel was associated with all oxidatively modified guanosine measures, whereas urinary chromium as well as nickel showed associations with urinary modified guanosines. In summary, oxidatively damaged urinary guanosine was associated with airborne and systemic exposure to metals in welders and showed a strong relation to body iron stores.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-014-1319-2) contains supplementary material, which is available to authorized users.

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

Abstract: 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.

Cited by 25 publications

References 64 publications

Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects

Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects

Base excision repair and cancer

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores

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