title: Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repair.
abstract: Lead is still widely used in many industrial processes and is very persistent in the environment. Although toxic effects caused by occupational exposure to lead have been extensively studied, there are still conflicting results regarding its genotoxicity. In a previous pilot study we observed some genotoxic effects in a population of lead exposed workers. Thus, we extended our study analysing a larger population, increasing the number of genotoxicity endpoints, and including a set of 20 genetic polymorphisms related to lead toxicokinetics and DNA repair as susceptibility biomarkers. Our population comprised 148 workers from two Portuguese factories and 107 controls. The parameters analysed were: blood lead levels (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity as exposure biomarkers, and T-cell receptor (TCR) mutation assay, micronucleus (MN) test, comet assay and OGG1-modified comet assay as genotoxicity biomarkers. Lead exposed workers showed markedly higher BLL and lower ALAD activity than the controls, and significant increases of TCR mutation frequency (TCR-Mf), MN rate and DNA damage. Oxidative damage did not experience any significant alteration in the exposed population. Besides, significant influence was observed for VDR rs1544410 polymorphism on BLL; APE1 rs1130409 and LIG4 rs1805388 polymorphisms on TCR-Mf; MUTYH rs3219489, XRCC4 rs28360135 and LIG4 rs1805388 polymorphisms on comet assay parameter; and OGG1 rs1052133 and XRCC4 rs28360135 polymorphisms on oxidative damage. Our results showed genotoxic effects related to occupational lead exposure to levels under the Portuguese regulation limit of 70 μg/dl. Moreover, a significant influence of polymorphisms in genes involved in DNA repair on genotoxicity biomarkers was observed.
authors.affiliation: Toxicology Unit, Department of Psychobiology, University of A Coruña, Edificio de Servicios Centrales de Investigación, Campus Elviña, 15071-A Coruña, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: García-Lestón
authors.forename: Joana
authors.initials: J
authors.lastname: Roma-Torres
authors.forename: Maria
authors.initials: M
authors.lastname: Vilares
authors.forename: Rui
authors.initials: R
authors.lastname: Pinto
authors.forename: João
authors.initials: J
authors.lastname: Prista
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Teixeira
authors.forename: Olga
authors.initials: O
authors.lastname: Mayan
authors.forename: João
authors.initials: J
authors.lastname: Conde
authors.forename: Marta
authors.initials: M
authors.lastname: Pingarilho
authors.forename: Jorge Francisco
authors.initials: JF
authors.lastname: Gaspar
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pásaro
authors.forename: Josefina
authors.initials: J
authors.lastname: Méndez
authors.forename: Blanca
authors.initials: B
authors.lastname: Laffon
mesh_terms: D000328:Adult; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D006801:Humans; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D009154:Mutation; D059645:Mutation Rate; D016273:Occupational Exposure / Q000706:statistics & numerical data*; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004785:Environmental Pollutants; D009153:Mutagens; C101467:XRCC4 protein, human; D007854:Lead; D000623:Porphobilinogen Synthase