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Genome-wide evidences of bisphenol a toxicity using Schizosaccharomyces pombe

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Abstract

To clarify reliable toxic mechanisms of bisphenol A (BPA), an endocrine disrupting chemical, we approached an alternative animal and whole genome analyses with the yeast knockout library (YKO) of Schizosaccharomyces pombe. As results, the 50% growth inhibition concentrations (GI50) of BPA was approximately 600 μM and the YKO—three step screening revealed the top 10 target candidate genes including dbp2, utp18, srs1, tif224, use1, qcr1, etc. The screening results were confirmed in human embryonic stem cell (hES)-derived hepatic cells and HepG2 human liver cancer cells. We found BPA down-regulated UQCRC, the human orthlog of S. pombe- qcr1, as a part of the mitochondrial respiratory chain, in HepG2 cells and hESs during cell differentiation into hepatic cells. Therefore, BPA may induce mitochondrial dysfunction and disruption of differentiation by suppressing UQCRC1.

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Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (No. 2011-0030074).

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Authors and Affiliations

  1. GPScreen Team, Bioneer Corporation, Daejeon, Republic of Korea

    Dong-Myung Kim

  2. Department of Molecular Biology and Immunology, College of Medicine, Kosin University, Busan, Republic of Korea

    Jeonghoon Heo

  3. Department of Bioengineering, Konyang University, Daejeon, Republic of Korea

    Dong Woo Lee

  4. Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Mayumi Tsuji

  5. Research Institute of Pharmaceutical Sciences (RIPS), Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women’s University, Cheongpa-ro 47-gil 100, Yongsan-gu, Seoul, 04310, Republic of Korea

    Mihi Yang

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  1. Dong-Myung Kim
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Correspondence to Mihi Yang.

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Kim, DM., Heo, J., Lee, D.W. et al. Genome-wide evidences of bisphenol a toxicity using Schizosaccharomyces pombe. Arch. Pharm. Res. 41, 830–837 (2018). https://doi.org/10.1007/s12272-018-1058-7

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