title: Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver.
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.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Kwang Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Jeong Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Ji Heon
authors.initials: JH
authors.lastname: Noh
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Eun
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Bae
authors.forename: Min Gyu
authors.initials: MG
authors.lastname: Kim
authors.forename: Young Gyoon
authors.initials: YG
authors.lastname: Chang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Shen
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kwon
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
mesh_terms: D000818:Animals; D015415:Biomarkers; D016000:Cluster Analysis; D004785:Environmental Pollutants / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D015870:Gene Expression; D020869:Gene Expression Profiling; D007928:Lethal Dose 50; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D047492:Peroxisome Proliferator-Activated Receptors; D011084:Polycyclic Aromatic Hydrocarbons