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

Emilene Arusievicz Nunes; Heliton Camargo da Silva; Nathália de Assis Aguilar Duarte; Lindiane Eloisa de Lima; Flora Troina Maraslis; Marília Ladeira de Araújo; Tatiana Pedron; Camila Neves Lange; Bruna Moreira Freire; Andreza Cândido Matias; Bruno Lemos Batista; Gustavo Rafael Mazzaron Barcelos

doi:10.1016/j.chemosphere.2023.138897

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

Chemosphere. 2023 Sep:334:138897. doi: 10.1016/j.chemosphere.2023.138897. Epub 2023 May 12.

Affiliations

¹ Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, CEP 11.060-001, Santos, Brazil. Electronic address: emilenean@gmail.com.
² Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, CEP 11.060-001, Santos, Brazil. Electronic address: heliton.cam@hotmail.com.
³ Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, CEP 11.060-001, Santos, Brazil. Electronic address: nathaliaduarte@hotmail.com.br.
⁴ Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, CEP 11.060-001, Santos, Brazil. Electronic address: lindianeeloisa@hotmail.com.
⁵ Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, CEP 11.060-001, Santos, Brazil. Electronic address: floratmaraslis@gmail.com.
⁶ Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, CEP 11.060-001, Santos, Brazil. Electronic address: ladeira.araujo@gmail.com.
⁷ Center of Natural and Human Sciences, Federal University of ABC, Avenida Dos Estados, 5001, CEP 09210-580, Santo André, Brazil. Electronic address: t.pedron@ufabc.edu.br.
⁸ Center of Natural and Human Sciences, Federal University of ABC, Avenida Dos Estados, 5001, CEP 09210-580, Santo André, Brazil. Electronic address: camilosalange@yahoo.com.
⁹ Center of Natural and Human Sciences, Federal University of ABC, Avenida Dos Estados, 5001, CEP 09210-580, Santo André, Brazil. Electronic address: bruna_231@hotmail.com.
¹⁰ Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, 1524, CEP 05508-000, São Paulo, Brazil. Electronic address: andreza.cmatias@hotmail.com.
¹¹ Center of Natural and Human Sciences, Federal University of ABC, Avenida Dos Estados, 5001, CEP 09210-580, Santo André, Brazil. Electronic address: bruno.lemos@ufabc.edu.br.
¹² Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua XV de Novembro 195, CEP 11.060-001, Santos, Brazil. Electronic address: gustavo.barcelos@unifesp.edu.br.

PMID: 37182709
DOI: 10.1016/j.chemosphere.2023.138897

Abstract

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.

Keywords: Blood lead levels; DNA damage; Micronucleus assay; Mutagenicity; Occupational exposure.

MeSH terms

Adult
Biomarkers
Cross-Sectional Studies
DNA Damage
DNA Repair
Humans
Lead* / toxicity
Male
Occupational Exposure* / adverse effects
Polymorphism, Single Nucleotide
X-ray Repair Cross Complementing Protein 1 / genetics

Substances

Lead
Biomarkers
XRCC1 protein, human
X-ray Repair Cross Complementing Protein 1