Cargando…

Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells

BACKGROUND: Lead (Pb) is a widely used metal in modern industry and is regarded as a health hazard. Although lead-induced genotoxicity has been confirmed, the direct evidence that lead induces genotoxicity in human cells and its related mechanisms has not been fully elucidated. In this study, for th...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Xiangquan, Wu, Jingying, Shi, Wenyan, Shi, Wenhua, Liu, Hekun, Wu, Xiaonan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045917/
https://www.ncbi.nlm.nih.gov/pubmed/29933360
http://dx.doi.org/10.12659/MSM.908425
_version_ 1783339752254078976
author Liu, Xiangquan
Wu, Jingying
Shi, Wenyan
Shi, Wenhua
Liu, Hekun
Wu, Xiaonan
author_facet Liu, Xiangquan
Wu, Jingying
Shi, Wenyan
Shi, Wenhua
Liu, Hekun
Wu, Xiaonan
author_sort Liu, Xiangquan
collection PubMed
description BACKGROUND: Lead (Pb) is a widely used metal in modern industry and is regarded as a health hazard. Although lead-induced genotoxicity has been confirmed, the direct evidence that lead induces genotoxicity in human cells and its related mechanisms has not been fully elucidated. In this study, for the first time, we evaluated the genotoxicity induced by lead in human lymphoblastoid TK6 cells. MATERIAL/METHODS: The TK6 cells were incubated with various concentrations of Pb(Ac)(2) for 6 h, 12 h, or 24 h. Cell viability was detected by CCK8 assay. Various biochemical markers were assessed by specific kits. Immunofluorescence assay was used to detect γ-H2AX foci formation. The promoter methylation was assessed by methylation-specific PCR. The protein levels were determined by Western blot assay. RESULTS: The results showed that after exposure to lead, cell viability was obviously decreased and γ-H2AX foci formation was significantly enhanced in TK6 cells. Moreover, the levels of 8-OHdG, ROS, MDA, and GSSG were increased, while the GSH level and SOD activity were decreased in lead-treated TK6 cells. The activation of the Nrf2-ARE signaling pathway was involved in lead-induced oxidative stress in TK6 cells. Finally, the expressions of DNA repair genes XRCC1, hOGG-1, BRCA1, and XPD were inhibited via enhancing their promoter methylation in TK6 cells after exposure to lead. CONCLUSIONS: Taken together, our study provides the first published evidence that lead exposure results in DNA damage via promoting oxidative stress and the promoter methylation of DNA repair genes in human lymphoblastoid TK6 cells.
format Online
Article
Text
id pubmed-6045917
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher International Scientific Literature, Inc.
record_format MEDLINE/PubMed
spelling pubmed-60459172018-07-17 Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells Liu, Xiangquan Wu, Jingying Shi, Wenyan Shi, Wenhua Liu, Hekun Wu, Xiaonan Med Sci Monit Lab/In Vitro Research BACKGROUND: Lead (Pb) is a widely used metal in modern industry and is regarded as a health hazard. Although lead-induced genotoxicity has been confirmed, the direct evidence that lead induces genotoxicity in human cells and its related mechanisms has not been fully elucidated. In this study, for the first time, we evaluated the genotoxicity induced by lead in human lymphoblastoid TK6 cells. MATERIAL/METHODS: The TK6 cells were incubated with various concentrations of Pb(Ac)(2) for 6 h, 12 h, or 24 h. Cell viability was detected by CCK8 assay. Various biochemical markers were assessed by specific kits. Immunofluorescence assay was used to detect γ-H2AX foci formation. The promoter methylation was assessed by methylation-specific PCR. The protein levels were determined by Western blot assay. RESULTS: The results showed that after exposure to lead, cell viability was obviously decreased and γ-H2AX foci formation was significantly enhanced in TK6 cells. Moreover, the levels of 8-OHdG, ROS, MDA, and GSSG were increased, while the GSH level and SOD activity were decreased in lead-treated TK6 cells. The activation of the Nrf2-ARE signaling pathway was involved in lead-induced oxidative stress in TK6 cells. Finally, the expressions of DNA repair genes XRCC1, hOGG-1, BRCA1, and XPD were inhibited via enhancing their promoter methylation in TK6 cells after exposure to lead. CONCLUSIONS: Taken together, our study provides the first published evidence that lead exposure results in DNA damage via promoting oxidative stress and the promoter methylation of DNA repair genes in human lymphoblastoid TK6 cells. International Scientific Literature, Inc. 2018-06-22 /pmc/articles/PMC6045917/ /pubmed/29933360 http://dx.doi.org/10.12659/MSM.908425 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Liu, Xiangquan
Wu, Jingying
Shi, Wenyan
Shi, Wenhua
Liu, Hekun
Wu, Xiaonan
Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells
title Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells
title_full Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells
title_fullStr Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells
title_full_unstemmed Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells
title_short Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells
title_sort lead induces genotoxicity via oxidative stress and promoter methylation of dna repair genes in human lymphoblastoid tk6 cells
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045917/
https://www.ncbi.nlm.nih.gov/pubmed/29933360
http://dx.doi.org/10.12659/MSM.908425
work_keys_str_mv AT liuxiangquan leadinducesgenotoxicityviaoxidativestressandpromotermethylationofdnarepairgenesinhumanlymphoblastoidtk6cells
AT wujingying leadinducesgenotoxicityviaoxidativestressandpromotermethylationofdnarepairgenesinhumanlymphoblastoidtk6cells
AT shiwenyan leadinducesgenotoxicityviaoxidativestressandpromotermethylationofdnarepairgenesinhumanlymphoblastoidtk6cells
AT shiwenhua leadinducesgenotoxicityviaoxidativestressandpromotermethylationofdnarepairgenesinhumanlymphoblastoidtk6cells
AT liuhekun leadinducesgenotoxicityviaoxidativestressandpromotermethylationofdnarepairgenesinhumanlymphoblastoidtk6cells
AT wuxiaonan leadinducesgenotoxicityviaoxidativestressandpromotermethylationofdnarepairgenesinhumanlymphoblastoidtk6cells