title: Characteristic molecular signature for early detection and prediction of persistent organic pollutants in rat liver.
abstract: Persistent organic pollutants (POPs) are degradation-resistant anthropogenic chemicals that accumulate in the food chain and in adipose tissue, and are among the most hazardous compounds ever synthesized. However, their toxic mechanisms are still undefined. To investigate whether characteristic molecular signatures can discriminate individual POP and provide prediction markers for the early detection of POPs exposure in an animal model, we performed transcriptomic analysis of rat liver tissues after exposure to POPs. The six different POPs (toxaphene, hexachlorobenzene, chlordane, mirex, dieldrin, and heptachlor) were administered to 11-week-old male Sprague-Dawley rats, and after 48 h of exposure, RNAs were extracted from liver tissues and subjected to rat whole genome expression microarrays. Early during exposure, conventional toxicological analysis including changes in the body and organ weight, histopathological examination, and blood biochemical analysis did not reflect any toxicant stresses. However, unsupervised gene expression analysis of rat liver tissues revealed in a characteristic molecular signature for each toxicant, and supervised analysis identified 2708 outlier genes that discerned the POPs exposure group from the vehicle-treated control. Combination analysis of two different multiclassifications suggested 384 genes as early detection markers for predicting each POP exposure with 100% accuracy. The data from large-scale gene expression analysis of a different POP exposure in rat model suggest that characteristic expression profiles exist in liver hepatic cells and multiclassification of POP-specific molecular signatures can discriminate each toxicant at an early exposure time. The use of these molecular markers may be more widely implemented in combination with more traditional techniques for assessment and prediction of toxicity exposure to POPs from an environmental aspect.
authors.affiliation: Department of Pathology, College of Medicine and Functional RNomics Research Center, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Kwang Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Jeong Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Min Gyu
authors.initials: MG
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: Young Gyoon
authors.initials: YG
authors.lastname: Chang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Shen
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; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004026:Dieldrin / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005659:Fungicides, Industrial / Q000633:toxicity; D006533:Heptachlor / Q000633:toxicity; D006581:Hexachlorobenzene / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008917:Mirex / Q000633:toxicity; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014112:Toxaphene / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D004785:Environmental Pollutants; D005659:Fungicides, Industrial; D007306:Insecticides; D010575:Pesticides; D006581:Hexachlorobenzene; D006533:Heptachlor; D014112:Toxaphene; D004026:Dieldrin; D008917:Mirex