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Prenatal Arsenic Exposure and Shifts in the Newborn Proteome: Interindividual Differences in Tumor Necrosis Factor (TNF)-Responsive Signaling


Bailey, Kathryn A.; Laine, Jessica E.; Rager, Julia E.; Sebastian, Elizabeth; Olshan, Andrew F.; Smeester, Lisa; Drobna, Zuzana; Styblo, Miroslav; Rubio-Andrade, Marisela; & Garcia-Vargas, Gonzalo G., et al. (2014). Prenatal Arsenic Exposure and Shifts in the Newborn Proteome: Interindividual Differences in Tumor Necrosis Factor (TNF)-Responsive Signaling. Toxicological Sciences, 139(2), 328-337. PMCID: PMC4031624


Exposure to inorganic arsenic (iAs) early in life is associated with adverse health effects in infants, children, and adults, and yet the biological mechanisms that underlie these effects are understudied. The objective of this research was to examine the proteomic shifts associated with prenatal iAs exposure using cord blood samples isolated from 50 newborns from Gomez Palacio, Mexico. Levels of iAs in maternal drinking water (DW-iAs) and the sum of iAs and iAs metabolites in maternal urine (U-tAs) were determined. Cord blood samples representing varying iAs exposure levels during the prenatal period (DW-iAs ranging from <1 to 236 mug As/L) were analyzed for altered expression of proteins associated with U-tAs using a high throughput, antibody-based method. A total of 111 proteins were identified that had a significant association between protein level in newborn cord blood and maternal U-tAs. Many of these proteins are regulated by tumor necrosis factor (TNF) and are enriched in functionality related to immune/inflammatory response and cellular development/proliferation. Inter-individual differences in proteomic response were observed in which 30 newborns were "activators," displaying a positive relationship between protein expression and maternal U-tAs. For 20 "repressor" newborns, a negative relationship between protein expression level and maternal U-tAs was observed. The activator/repressor status was significantly associated with maternal U-tAs and head circumference in newborn males. These results may provide a critical groundwork for understanding the diverse health effects associated with prenatal arsenic exposure and highlight inter-individual responses to arsenic that likely influence susceptibility to adverse health outcomes.


Reference Type

Journal Article

Year Published


Journal Title

Toxicological Sciences


Bailey, Kathryn A.
Laine, Jessica E.
Rager, Julia E.
Sebastian, Elizabeth
Olshan, Andrew F.
Smeester, Lisa
Drobna, Zuzana
Styblo, Miroslav
Rubio-Andrade, Marisela
Garcia-Vargas, Gonzalo G.
Fry, Rebecca C.