Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repair |
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| Affiliation: | 1. Toxicology Unit, Department of Psychobiology, University of A Coruña, Edificio de Servicios Centrales de Investigación, Campus Elviña, 15071-A Coruña, Spain;2. Department of Cell and Molecular Biology, University of A Coruña, Facultad de Ciencias, Campus da Zapateira, 15071-A Coruña, Spain;3. National Institute of Health, Environmental Health Department, Rua Alexandre Herculano 321, 4000-055-Porto, Portugal;4. Escola Nacional de Saúde Pública, Universidade Nova de Lisboa, Av. Padre Cruz, 1600-560 Portugal;5. National Institute of Health, Department of Health and health-promoting chronic diseases, Unit of Research and Development, Av. Padre Cruz, 1649-061 Lisboa, Portugal;6. iMed.UL, Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal;7. Department of Genetics, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua da Junqueira 100, P-1349-008 Lisbon, Portugal;1. Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia;2. Department of Chemistry, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia;3. ICTM Department of Chemistry, University of Belgrade, Belgrade, Serbia;4. Institute of Occupational Health of Serbia “Dr Dragomir Karajovi?”, Belgrade, Serbia;5. Laboratory for Radiobiology and Molecular Genetics, Institute for Nuclear Research “Vinca”, University of Belgrade, Serbia;1. Department of Medical-Surgical Nursing, School of Nursing, Universidade de São Paulo, São Paulo 05403 000, Brazil;2. Department of Psychobiology, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil;3. Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, United States;4. Centre for Studies on Human Stress, Mental Health University Institute, Department of Psychiatry, University of Montreal, QC, Canada H1N 3V2;5. School of Psychoeducation, Université de Montréal, Montreal, QC, Canada J1K 2R1;6. Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040903, Brazil;7. Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo 05508-000, Brazil;1. Departamento de Biofísica, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil;2. Unidad de Investigación, Desarrollo e Innovación en Genética y Biología Molecular, Universidad Simón Bolívar, Barranquilla, Colombia;3. Laboratório de Implantação Iônica, Instituto de Física, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil;4. Laboratorio de Investigación Biomédica y Biología Molecular, Universidad del Sinú, Montería, Colombia;5. Novartis Pharma AG, Basel, Switzerland;6. Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brasil;7. Laboratório de Genética Toxicológica, Universidade Luterana do Brasil (ULBRA), Canoas-RS, Brasil;1. Department of Epidemiology, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA;2. Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA |
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| 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 70μg/dl. Moreover, a significant influence of polymorphisms in genes involved in DNA repair on genotoxicity biomarkers was observed. |
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