Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver

Kwang Hwa Jung, Jeong Kyu Kim, Ji Heon Noh, Jung Woo Eun, Hyun Jin Bae, Min Gyu Kim, Young Gyoon Chang, Qingyu Shen, Seung Jin Kim, So Hee Kwon, Won Sang Park, Jung Young Lee, Suk Woo Nam

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Abstract

Predictions of toxicity are central for the assessment of chemical toxicity, and the effects of environmental toxic compounds are still a major issue for predicting potential human health risks. Among the various environmental toxicants, polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutant, and many PAHs are known or suspected carcinogens. In the present study, to investigate whether characteristic expression profiles of PAHs exist in rat liver and whether a characteristic molecular signature can discriminate and predict among different PAHs at an early exposure time, we analyzed the genome-wide expression profiles of rat livers exposed to PAHs [benzo[a]anthracene (BA), benzo[a]pyrene (BP), phenanthrene (PA) and naphthalene (NT)]. At early time-point PAH exposure, large-scale gene expression analysis resulted in characteristic molecular signatures for each PAH, and supervised analysis identified 1183 outlier genes as a distinct molecular signature discerning PAHs from the normal control group. We identified 158 outlier genes as early predictive and surrogate markers for predicting each tested PAH by combination of two different multi-classification algorithms with 100% accuracy through a leave-one out cross-validation method. In conclusion, the characteristic gene expression signatures from a rat model system could be used as predictable and discernible gene-based biomarkers for the detection and prediction of PAHs, and these molecular markers may provide insights into the underlying mechanisms for genotoxicity of exposure to PAHs from environmental aspect.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalToxicology Letters
Volume216
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

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All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Jung, K. H., Kim, J. K., Noh, J. H., Eun, J. W., Bae, H. J., Kim, M. G., Chang, Y. G., Shen, Q., Kim, S. J., Kwon, S. H., Park, W. S., Lee, J. Y., & Nam, S. W. (2013). Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver. Toxicology Letters, 216(1), 1-8. https://doi.org/10.1016/j.toxlet.2012.11.001