Activation of Inflammation/NF-κB Signaling in Infants Born to Arsenic-Exposed Mothers
Rebecca C. Fry1,2
, Panida Navasumrit3, Chandni Valiathan1,2, J. Peter Svensson1,2, Bradley J. Hogan1,2, Manlin Luo1,2, Sanchita Bhattacharya1,2¤, Krittinee Kandjanapa3, Sumitra Soontararuks3, Sumontha Nookabkaew3, Chulabhorn Mahidol3, Mathuros Ruchirawat3*, Leona D. Samson1,2*
1 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 2 Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3 Chulabhorn Research Institute, Bangkok, Thailand
The long-term health outcome of prenatal exposure to arsenic has been associated with increased mortality in human populations. In this study, the extent to which maternal arsenic exposure impacts gene expression in the newborn was addressed. We monitored gene expression profiles in a population of newborns whose mothers experienced varying levels of arsenic exposure during pregnancy. Through the application of machine learning–based two-class prediction algorithms, we identified expression signatures from babies born to arsenic-unexposed and -exposed mothers that were highly predictive of prenatal arsenic exposure in a subsequent test population. Furthermore, 11 transcripts were identified that captured the maximal predictive capacity to classify prenatal arsenic exposure. Network analysis of the arsenic-modulated transcripts identified the activation of extensive molecular networks that are indicative of stress, inflammation, metal exposure, and apoptosis in the newborn. Exposure to arsenic is an important health hazard both in the United States and around the world, and is associated with increased risk for several types of cancer and other chronic diseases. These studies clearly demonstrate the robust impact of a mother's arsenic consumption on fetal gene expression as evidenced by transcript levels in newborn cord blood.
Funding. This work was supported by grants ES11399 and ES002109.
Competing interests. The authors have declared that no competing interests exist.
Editor: Vivian G. Cheung, University of Pennsylvania, United States of America
Citation: Fry RC, Navasumrit P, Valiathan C, Svensson JP, Hogan BJ, et al. (2007) Activation of Inflammation/NF-κB Signaling in Infants Born to Arsenic-Exposed Mothers. PLoS Genet 3(11): e207 doi:10.1371/journal.pgen.0030207
Received: July 4, 2007; Accepted: October 4, 2007; Published: November 23, 2007
Copyright: © 2007 Fry et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abbreviations: FDR, false discovery rate; GSEA, Gene Set Enrichment Analysis; WHO, World Health Organization
* To whom correspondence should be addressed. E-mail: lsamson@mit.edu; mathuros@cri.or.th
These authors contributed equally to this work.
¤ Current address: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America
