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KMID : 1034820170130020179
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Molecular & Cellular Toxicology
2017 Volume.13 No. 2 p.179 ~ p.188
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Integrative toxicogenomic analysis for elucidating molecular interference on DNA integrity and repair system with underlying signaling networks in response to low-level lead acetate in rat liver model
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Kim Hyun-Soo
Lee Sang-Min
Kim Yeo-Jin
Jang Won-Hee
Seo Young-Rok
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Abstract
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Lead (Pb) is widely used in consumer products as an alloy and pigment despite its well-known serious toxic effects. Pb absorbed through the gastrointestinal and respiratory system flows through the bloodstream and accumulates in the brain, bone and liver. Especially, the liver is well known as an important organ for detoxification, and a number of prior studies have confirmed the alteration of diverse biological mechanisms caused by long-term Pb exposure in the liver. In this study, we investigated the genotoxic potential of Pb on nuclear DNA and repair capacity using comet and AP endonuclease activity assay, respectively in rat liver tissue at long-term and low-level exposure. Significant extent of DNA break damages and the impairment of enzymatic repair activities were observed in the Pb exposed group, in comparison to the control group. In addition, using integrative toxicogenomic approach we comprehensively analyzed the Pb-induced gene alteration in genome-wide scale and DNA excision repair-focused biological networks using microarray and pathway analysis, respectively. Based on integrative approach, we suggest that genotoxic effects of low-level Pb exposure are, in part, involved in the enhancement of DNA strand break and impairment of repair activity, with complex molecular signaling pathways. Our study provides perspective on novel biomarker responsible for Pb-induced hepatotoxicity at long-term and low-dose exposure, which would be useful for further development of gene-targeted therapeutic strategies and/or natural chemo-preventive agents for effective reduction of the Pb toxicity in both occupational and environmental perspectives. The exact mechanism of genotoxicity in liver exposed to low-level Pb will be further warranted.
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KEYWORD
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Lead, DNA repair, Genotoxicity, Pathway analysis, Toxicogenomics
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