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Gene expression analysis identifies DNA damage-related markers of benzo[a]pyrene exposure in HepG2 human hepatocytes

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Abstract

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is carcinogenic to humans. Although the environmental distribution and metabolism of BaP have been reported and many researchers are performing risk-assessment and toxicological studies of BaP by means of physical and chemical measurements, only a few studies have examined the expression of mRNAs and their functions in BaP-induced toxicity. Toxicogenomic technology, a new paradigm in toxicity screening, is a useful approach for evaluating the toxic properties of environmental pollutants. We analyzed gene expression profiles using human oligonucleotide chips and identified genes in human hepatocellular carcinoma (HepG2) cells whose expression changed > 1.5-fold after exposure to BaP. The expression of 4,048 and 3,926 genes was up-and down-regulated > 1.5-fold (P < 0.01), respectively, after exposure. Gene ontology (GO) analysis of these genes revealed significant enrichment in several key biological processes related to DNA damage, including DNA repair, cell cycle arrest, and apoptosis. We also performed a contrastive study of cellular effects in HepG2 cells exposed to BaP, and identified increased expression of related genes, cell cycle arrest, and apoptotic cells. These results suggest that genetic markers of BaP-induced toxicity may be molecular blueprints that can be more widely implemented in combination with more traditional techniques for assessment and prediction.

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Authors and Affiliations

  1. Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul, 130-650, Korea

    Mi-Kyung Song, Ji-Seong Yoon, Mee Song, Han-Seam Choi, Chan-Young Shin, Woo-In Ryu, Hyo-Sun Lee & Jae-Chun Ryu

  2. Department of Food and Nutrition, Eulji University, 212 Yangji-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi, 461-713, Korea

    Youn-Jung Kim

Authors
  1. Mi-Kyung Song
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  2. Ji-Seong Yoon
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  4. Han-Seam Choi
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  5. Chan-Young Shin
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  7. Woo-In Ryu
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  9. Jae-Chun Ryu
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Correspondence to Jae-Chun Ryu.

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Song, MK., Yoon, JS., Song, M. et al. Gene expression analysis identifies DNA damage-related markers of benzo[a]pyrene exposure in HepG2 human hepatocytes. Toxicol. Environ. Health Sci. 4, 19–29 (2012). https://doi.org/10.1007/s13530-012-0118-5

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  • DOI: https://doi.org/10.1007/s13530-012-0118-5

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