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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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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Polycyclic Aromatic Hydrocarbons
Liver
Rats
Genes
Gene expression
Toxicity
Biomarkers
Environmental Pollutants
Poisons
Health risks
Benzo(a)pyrene
Transcriptome
Carcinogens
Genome
Gene Expression
Control Groups

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Jung, Kwang Hwa ; Kim, Jeong Kyu ; Noh, Ji Heon ; Eun, Jung Woo ; Bae, Hyun Jin ; Kim, Min Gyu ; Chang, Young Gyoon ; Shen, Qingyu ; Kim, Seung Jin ; Kwon, So Hee ; Park, Won Sang ; Lee, Jung Young ; Nam, Suk Woo. / Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver. In: Toxicology Letters. 2013 ; Vol. 216, No. 1. pp. 1-8.
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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.",
author = "Jung, {Kwang Hwa} and Kim, {Jeong Kyu} and Noh, {Ji Heon} and Eun, {Jung Woo} and Bae, {Hyun Jin} and Kim, {Min Gyu} and Chang, {Young Gyoon} and Qingyu Shen and Kim, {Seung Jin} and Kwon, {So Hee} and Park, {Won Sang} and Lee, {Jung Young} and Nam, {Suk Woo}",
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Jung, KH, Kim, JK, Noh, JH, Eun, JW, Bae, HJ, Kim, MG, Chang, YG, Shen, Q, Kim, SJ, Kwon, SH, Park, WS, Lee, JY & Nam, SW 2013, 'Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver', Toxicology Letters, vol. 216, no. 1, pp. 1-8. https://doi.org/10.1016/j.toxlet.2012.11.001

Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver. / Jung, Kwang Hwa; Kim, Jeong Kyu; Noh, Ji Heon; Eun, Jung Woo; Bae, Hyun Jin; Kim, Min Gyu; Chang, Young Gyoon; Shen, Qingyu; Kim, Seung Jin; Kwon, So Hee; Park, Won Sang; Lee, Jung Young; Nam, Suk Woo.

In: Toxicology Letters, Vol. 216, No. 1, 01.01.2013, p. 1-8.

Research output: Contribution to journalArticle

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AU - Jung, Kwang Hwa

AU - Kim, Jeong Kyu

AU - Noh, Ji Heon

AU - Eun, Jung Woo

AU - Bae, Hyun Jin

AU - Kim, Min Gyu

AU - Chang, Young Gyoon

AU - Shen, Qingyu

AU - Kim, Seung Jin

AU - Kwon, So Hee

AU - Park, Won Sang

AU - Lee, Jung Young

AU - Nam, Suk Woo

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