Abstract

The aim of the study was to examine the association between polymorphisms of DNA repair genes and chromosomal damage of 1,3-butadiene- (BD-) exposed workers. The study was conducted in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and a circulatory water workshop in China. Newly developed biomarkers (micronuclei, MNi; nucleoplasmic bridges, NPBs; nuclear buds, NBUDs) in the cytokinesis-blocked micronucleus (CBMN) cytome assay were adopted to detect chromosomal damage. PCR and PCR-restriction fragment length polymorphism (RFLP) are adopted to analyze polymorphisms of DNA repair genes, such as X-ray repair cross-complementing Group 1 (XRCC1), O6-methylguanine-DNA methyltransferase (MGMT), poly (adenosine diphosphate-ribose) polymerases (ADPRT), and apurinic/apyrimidinic endonucleases (APE1). The BD-exposed workers exhibited increased frequencies of MNi and NPBs when compared to subjects in the control group. The results also show that the BD-exposed workers carrying XRCC1 diplotypes TCGA-CCGG (4.25 ± 2.06‰) (FR = 2.10, 95% CI: 1.03–4.28) and TCGG-TCGA (5.80 ± 3.56‰) (FR = 2.75, 95% CI: 0.76–2.65) had statistically higher NBUD frequencies than those who carried diplotype TCGG-TCGG (1.89 ± 1.27‰). Our study suggests that polymorphisms of XRCC1 gene may influence chromosomal damage in BD-exposed workers.

Highlights

  • 1,3-Butadiene (BD), a Group 1 carcinogen as classified by IARC in 2008 [1], is widely used as an industrial chemical and is present in autoemission and tobacco smoke [2]

  • In 2009, using cytokinesisblocked micronucleus (CBMN) cytome assay, we found that BD-exposed workers exhibited increased frequencies of micronuclei (MNi) and nucleoplasmic bridges (NPBs) when compared to subjects in the control group

  • The research conducted on workers employed in tire plants of the Czech Republic did not find any significant association between genetic polymorphism of X-ray repair cross-complementing Group 1 (XRCC1) exon 10 (Arg399Gln) and DNA damage biomarkers including chromosome aberrations and single strand breaks, where these workers were exposed to a variety of xenobiotics, the most prominent being BD and soot containing polycyclic aromatic hydrocarbons (PAHs) [19]

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Summary

Introduction

1,3-Butadiene (BD), a Group 1 carcinogen as classified by IARC in 2008 [1], is widely used as an industrial chemical and is present in autoemission and tobacco smoke [2]. The research conducted on workers employed in tire plants of the Czech Republic did not find any significant association between genetic polymorphism of XRCC1 exon 10 (Arg399Gln) and DNA damage biomarkers including chromosome aberrations and single strand breaks, where these workers were exposed to a variety of xenobiotics, the most prominent being BD and soot containing polycyclic aromatic hydrocarbons (PAHs) [19]. These inconsistent results indicated that the polymorphisms of XRCC1 gene and associated DNA repair genes are worthy of further research to clarify their roles in BD-related genotoxicity. The MGMT protein can rapidly reverse alkylation at the O6 position of guanine, thereby averting the formation of lethal cross-links [20]

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