Identification of characteristic molecular signature for volatile organic compounds in peripheral blood of rat.
In a previous report we demonstrated that the transcriptomic response of liver tissue was specific to toxicants, and a characteristic molecular signature could be used as an early prognostic biomarker in rats. It is necessary to determine the transcriptomic response to toxicants in peripheral blood for application to the human system. Volatile organic compounds (VOCs) comprise a major group of pollutants which significantly affect the chemistry of the atmosphere and human health. In this study we identified and validated the specific molecular signatures of toxicants in rat whole blood as early predictors of environmental toxicants. VOCs (dichloromethane, ethylbenzene, and trichloroethylene) were administered to 11-week-old SD male rats after 48h of exposure, peripheral whole blood was subjected to expression profiling analysis. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxicant, and supervised analysis identified 1,217 outlier genes as distinct molecular signatures discerning VOC exposure from healthy controls. Further analysis of multi-classification suggested 337 genes as early detective molecular markers for three VOCs with 100% accuracy. A large-scale gene expression analysis of a different VOC exposure animal model suggested that characteristic expression profiles exist in blood cells and multi-classification of this VOC-specific molecular signature can discriminate each toxicant at an early exposure time. This blood expression signature can thus be used as discernable surrogate marker for detection of biological responses to VOC exposure in an environment.
Department of Pathology, Microdissection Genomics Research Center (MGRC), College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
Jeong Kyu
JK
Kim
Kwang Hwa
KH
Jung
Ji Heon
JH
Noh
Jung Woo
JW
Eun
Hyun Jin
HJ
Bae
Hong Jian
HJ
Xie
Ja-June
JJ
Jang
Jae Chun
JC
Ryu
Won Sang
WS
Park
Jung Young
JY
Lee
Suk Woo
SW
Nam
D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008752:Methylene Chloride / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014241:Trichloroethylene / Q000633:toxicity*
D001555:Benzene Derivatives; D015415:Biomarkers; D014241:Trichloroethylene; D008752:Methylene Chloride; C004912:ethylbenzene