Activation of Inflammation/NF-κB Signaling in Infants Born to Arsenic-Exposed Mothers Published: Nov 23, 2007 - DOI: 10.1371/journal.pgen.0030207 Rebecca C Fry equal contributor, Panida Navasumrit equal contributor, Chandni Valiathan equal contributor, J. Peter Svensson, Bradley J Hogan, Manlin Luo, Sanchita Bhattacharya, Krittinee Kandjanapa, Sumitra Soontararuks, Sumontha Nookabkaew, Chulabhorn Mahidol, Mathuros Ruchirawat, Leona D Samson This study has permitted a better understanding of the impact of maternal arsenic exposure. Constant exposure to arsenic-contaminated water is an important public health hazard around the world. The results of this study put in evidence the alarming gene expression changes in new-born babies to arsenic-exposed mothers with in utero robust activation of inflammation, cell proliferation, stress and apoptosis with increased mortality rates. M e t h o d : This study was conducted in the Ron Pibul and Bangkok districts of Thailand in an arsenic contaminated region attributed to tin mining from 1960s to 1980s. (D) TNF-a–associated network composed of eight core members of the potential gene biomarkers for arsen exposure. Biomarker genes with binding sites for M transcription factor are indicated. Proteins in re e r e n c e : J.L. et al. (2003) Inhibition of NF-kappaB in cancer cells converts inflammation-induce tumo ted by TNF alpha to TRAIL-mediated tumors regression. Cancer cell, 2004:6:297-305 PubMed Figure 1. Gene Expression Signatures Predict Arsenic Exposure in Tests Population. (B) Expression values are mean centered with high relative expression indicated in red and low relative expression indicated in blue. Figure 2. Prenatal Arsenic Exposure Results in Robust Genome-W Changes response in the foetus and acts as an inflammatory sti That activates NF-kB, playing a critical role in inflammation- tumour progression (Luo,2003) Figure 3. Sub-networks of Prenatal Arsenic-Modulated Gene Products Apoptosis/stress response Signal transduction Lipid metabolism Transcription Cell adhesion (D) (C) -1, OSM, JUNB focused sub-network highlights numerous ogical processes modulated in response to arsenic. Proteins encoded by otential gene biomarkers for arsenic exposure are indicated with a *. Up-regulated ___________ rect intervention hosphatase G protein coupled receptor al horizontal Transcriptional regulator al vertical Transmembrane receptor ▀ Down-regulated - - - - - - - Indirect intervention ▀ Cytokinine ◊ ◊ Enzyme ▼▼ Kinase Trapezoid / Trapezoid Transporter ○ ○ Other Globally, millions of people exposed to arsenic ar contaminated and suffering. ◙ Because arsenic targ widely disperse enzymes reactions, it affects all systems according to the Agency for Toxic Substanc Glucose transport Brigitte-Karaja dyz Athlandys * * * *