Molecular signature for early detection and prediction of polycyclic aromatic hydrocarbons in peripheral blood.
Whole blood is one of the most easily accessible biofluids, and circulating leukocytes would include informative transcripts as a first line of immune defense for many disease processes. To demonstrate that transcriptomic responses of circulating blood cells reflect the exposure to environmental toxicants and the characteristic molecular signatures can discriminate and predict the type of toxicant at an early exposure time, we identified and validated characteristic gene expression profiles of rat whole blood after exposure to polycyclic aromatic hydrocarbons (PAHs). At an early exposure time point, 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 blood cells resulted in a characteristic molecular signature for each toxicant. Further analysis of multiclassification suggested 220 genes as early detective and surrogate markers for predicting each PAH with 100% accuracy. These findings suggest that the blood expression signature could be used as a predictable and discernible surrogate marker for detection and prediction of PAHs, and 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 PAHs from an environmental aspect.
Department of Pathology, College of Medicine and Microdissection Genomics Research Center, The Catholic University of Korea, Banpo-dong #505, Seocho-gu, Seoul 137-701, Republic of Korea.
Kwang Hwa
KH
Jung
Ji Heon
JH
Noh
Jung Woo
JW
Eun
Jeong Kyu
JK
Kim
Hyun Jin
HJ
Bae
Hongjian
H
Xie
Ja-June
JJ
Jang
Jae Chun
JC
Ryu
Won Sang
WS
Park
Jung Young
JY
Lee
Suk Woo
SW
Nam
D000818:Animals; D001551:Benz(a)Anthracenes / Q000097:blood / Q000633:toxicity; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D004781:Environmental Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000097:blood* / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D008297:Male; D009281:Naphthalenes / Q000097:blood / Q000633:toxicity; D010616:Phenanthrenes / Q000097:blood / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D001551:Benz(a)Anthracenes; D015415:Biomarkers; D004785:Environmental Pollutants; D009281:Naphthalenes; D010616:Phenanthrenes; D011084:Polycyclic Aromatic Hydrocarbons; C031721:naphthalene; D001564:Benzo(a)pyrene; C031181:phenanthrene; C030935:benz(a)anthracene