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Evaluating the Extent of LINE-1 Mobility Following Exposure to Heavy Metals in HepG2 Cells

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Abstract

The long interspersed elements-1 (LINE1 or L1 retrotransposon) constitute 17 % of the human genome and retain mobility properties within the genome. At present, 80–100 human L1 elements are thought to be active in the genome. The mobilization of these active elements may be influenced upon exposure to the heavy metals. In the present study, we evaluated the association of aluminum, lead, and copper exposure with L1 retrotransposition in human hepatocellular carcinoma (HepG2) cell line. An in vitro retrotransposition assay using an enhanced green fluorescent protein (EGFP)-tagged L1RP cassette was established to track EGFP shining as the mark of retrotransposition. Following determination of noncytotoxic concentrations of these metals, pL1RP-EGFP-transfected HepG2 cells were subjected to long-term treatment. Flow cytometry analysis of cells treated with various concentrations of these metals along with quantitative real-time PCR was used to quantify L1 retrotransposition frequencies. Aluminum significantly increased L1 retrotransposition frequency, while no significant association was found concerning lead exposure and L1 retrotransposition. Copper treatment downregulated L1 retrotransposition as a result of EGFP-tagged L1RP expression. Our findings suggest that aluminum might have the potential to cause genomic instability by the enhancement of L1 mobilization. Thus, the risk of induced L1 retrotransposition should be considered during drug safety evaluation and risk assessments of exposure to toxic environmental agents. Further studies are needed for a more robust assay to evaluate any associations between long-term lead exposure and L1 mobility in cell culture assay.

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Acknowledgments

The authors thank Tehran University of Medical Sciences for financial support of this project (Grant number. 17245). This study was conducted in the Cellular and Molecular Research Center (CMRC) of Iran University of Medical Sciences as part of a PhD dissertation. Our special thanks are extended to the staff of CMRC for their technical support. The authors would also like to acknowledge with much appreciation the crucial role of Mr. Mohammad Yahya Karimi in Razi Drug Research Center, who was abundantly helpful and offered invaluable assistance and guidance.

Conflict of Interest

No competing financial interests exist.

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Authors and Affiliations

  1. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine (FATiM), Iran University of Medical Sciences, Tehran, Iran

    Abbas Karimi & Zahra Madjd

  2. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Abbas Karimi & Zahra Madjd

  3. Oncopathology Research Centre, Iran University of Medical Sciences, Tehran, Iran

    Zahra Madjd

  4. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina St., Tehran, Iran

    Laleh Habibi & Seyed Mohammad Akrami

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  1. Abbas Karimi
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Correspondence to Zahra Madjd or Seyed Mohammad Akrami.

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Karimi, A., Madjd, Z., Habibi, L. et al. Evaluating the Extent of LINE-1 Mobility Following Exposure to Heavy Metals in HepG2 Cells. Biol Trace Elem Res 160, 143–151 (2014). https://doi.org/10.1007/s12011-014-0015-7

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  • DOI: https://doi.org/10.1007/s12011-014-0015-7

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