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 arsenic exposure. Biomarker genes with binding sites for MTF transcription factor are indicated. Proteins in red

R e f e r e n c e :Luo, J.L. et al. (2003) Inhibition of NF-kappaB in cancer cells converts inflammation-induce tumor growthmediated 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-WideChanges response in the foetus and acts as an inflammatory stimulusThat activates NF-kB, playing a critical role in inflammation-driven 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)

(C) An EGR-1, OSM, JUNB focused sub-network highlights numerous biological processes modulated in response to arsenic. Proteins encoded by 11 potential gene biomarkers for arsenic exposure are indicated with a *.

▀ Up-regulated_____________Direct intervention▲Phosphatase█ G protein coupled receptorOval horizontal Transcriptional regulatorOval vertical Transmembrane receptor

▀ Down-regulated- - - - - - - Indirect intervention▀ Cytokinine◊ ◊ Enzyme▼▼ KinaseTrapezoid / Trapezoid Transporter○ ○ Other

Globally, millions of people exposed to arsenic are highly contaminated and suffering. ◙ Because arsenic targets widely disperse enzymes reactions, it affects all organ systems according to the Agency for Toxic Substances.

Glucose transport

Brigitte-Karaja dyz Athlandys

* * **