Impact of DNA repair polymorphisms on DNA instability biomarkers induced by lead (Pb) in workers exposed to the metal

被引:0
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作者
Nunes E.A. [1 ]
Silva H.C.D. [1 ]
Duarte N.D.A.A. [1 ]
de Lima L.E. [1 ]
Maraslis F.T. [1 ]
Araújo M.L.D. [1 ]
Pedron T. [2 ]
Neves Lange C. [2 ]
Freire B.M. [2 ]
Matias A.C. [3 ]
Batista B.L. [2 ]
Barcelos G.R.M. [1 ]
机构
[1] Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, Santos
[2] Center of Natural and Human Sciences, Federal University of ABC, Avenida Dos Estados, 5001, Santo André
[3] Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo
基金
巴西圣保罗研究基金会;
关键词
Blood lead levels; DNA damage; Micronucleus assay; Mutagenicity; Occupational exposure;
D O I
10.1016/j.chemosphere.2023.138897
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学科分类号
摘要
Although the mechanisms of Pb-induced genotoxicity are well established, a wide individual's variation response is seen in biomarkers related to Pb toxicity, despite similar levels of metal exposure. This may be related to intrinsic variations, such as genetic polymorphisms; moreover, very little is known about the impact of genetic variations related to DNA repair system on DNA instability induced by Pb. In this context, the present study aimed to assess the impact of SNPs in enzymes related to DNA repair system on biomarkers related to acute toxicity and DNA damage induced by Pb exposure, in individuals occupationally exposed to the metal. A cross-sectional study was run with 154 adults (males, >18 years) from an automotive batteries' factory, in Brazil. Blood lead levels (BLL) were determined by ICP-MS; biomarkers related to acute toxicity and DNA instability were monitored by the buccal micronucleus cytome (BMNCyt) assay and genotyping of polymorphisms of MLH1 (rs1799977), OGG1 (rs1052133), PARP1 (rs1136410), XPA (rs1800975), XPC (rs2228000) and XRCC1 (rs25487) were performed by TaqMan assays. BLL ranged from 2.0 to 51 μg dL−1 (mean 20 ± 12 μg dL−1) and significant associations between BLL and BMNCyt biomarkers related to cellular proliferation and cytokinetic, cell death and DNA damage were observed. Furthermore, SNPs from the OGG1, XPA and XPC genes were able to modulate interactions in nuclear bud formation (NBUDs) and micronucleus (MNi) events. Taken together, our data provide further evidence that polymorphisms related to DNA repair pathways may modulate Pb-induced DNA damage; studies that investigate the association between injuries to genetic material and susceptibilities in the workplace can provide additional information on the etiology of diseases and the determination of environmentally responsive genes. © 2023
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