@article{adebambo_shea_fry_2018, title={Cadmium disrupts signaling of the hypoxia-inducible (HIF) and transforming growth factor (TGF-beta) pathways in placental JEG-3 trophoblast cells via reactive oxygen species}, volume={342}, ISSN={["1096-0333"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85041525284&partnerID=MN8TOARS}, DOI={10.1016/j.taap.2018.01.010}, abstractNote={Epidemiologic studies indicate an association between exposure to cadmium (Cd) and placental-related pregnancy disorders. While a precise mechanism is unknown, oxidative imbalance and dysregulation of the hypoxia inducible factor (HIF) and transforming growth factor beta (TGF-β) pathways have been implicated in placental disease pathogenesis. Here we investigated key oxidative and placentation pathways in JEG-3 placental trophoblast cells treated with Cd alone, environmental water samples predominated by Cd with low concentrations of other metals (e.g. inorganic arsenic (iAs)) collected from a waste-site, and a matched mixture of Cd and iAs prepared in the laboratory. The induction of cytosolic reactive oxygen species (ROS), expression of metallothionein (MT) isoforms, HIF1α and downstream targets, and expression of TGFβ pathway-associated genes and proteins were assessed. Additionally, the effect of pre-treatment with the antioxidant N-acetyl cysteine (NAC) on ROS generation and effects on HIF, MT and TGF-β signaling pathways was examined. Cd and Cd-mixture treated cells displayed higher levels of ROSs with accompanying disruption of HIF and TGFβ pathway signaling versus controls, with the Cd-mixture eliciting a greater effect. Conversely, pretreatment with NAC reduced Cd-induced ROS production and disruption of HIF, MT and TGFβ pathway signaling. The results indicate that treatment of placental trophoblast cells with Cd results in increased production of ROSs that disrupt placentation pathways involved in disease pathogenesis. Also, co-occurrence of Cd with other toxic metals, particularly arsenic, may induce detrimental health effects that are currently underestimated when analyzed as single metals.}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Adebambo, Oluwadamilare A. and Shea, Damian and Fry, Rebecca C.}, year={2018}, month={Mar}, pages={108–115} }
 @article{adebambo_ray_shea_fry_2015, title={Toxicological responses of environmental mixtures: Environmental metal mixtures display synergistic induction of metal-responsive and oxidative stress genes in placental cells}, volume={289}, ISSN={["1096-0333"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84947768563&partnerID=MN8TOARS}, DOI={10.1016/j.taap.2015.10.005}, abstractNote={Exposure to elevated levels of the toxic metals inorganic arsenic (iAs) and cadmium (Cd) represents a major global health problem. These metals often occur as mixtures in the environment, creating the potential for interactive or synergistic biological effects different from those observed in single exposure conditions. In the present study, environmental mixtures collected from two waste sites in China and comparable mixtures prepared in the laboratory were tested for toxicogenomic response in placental JEG-3 cells. These cells serve as a model for evaluating cellular responses to exposures during pregnancy. One of the mixtures was predominated by iAs and one by Cd. Six gene biomarkers were measured in order to evaluate the effects from the metal mixtures using dose and time-course experiments including: heme oxygenase 1 (HO-1) and metallothionein isoforms (MT1A, MT1F and MT1G) previously shown to be preferentially induced by exposure to either iAs or Cd, and metal transporter genes aquaporin-9 (AQP9) and ATPase, Cu2 + transporting, beta polypeptide (ATP7B). There was a significant increase in the mRNA expression levels of ATP7B, HO-1, MT1A, MT1F, and MT1G in mixture-treated cells compared to the iAs or Cd only-treated cells. Notably, the genomic responses were observed at concentrations significantly lower than levels found at the environmental collection sites. These data demonstrate that metal mixtures increase the expression of gene biomarkers in placental JEG-3 cells in a synergistic manner. Taken together, the data suggest that toxic metals that co-occur may induce detrimental health effects that are currently underestimated when analyzed as single metals.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Adebambo, Oluwadamilare A. and Ray, Paul D. and Shea, Damian and Fry, Rebecca C.}, year={2015}, month={Dec}, pages={534–541} }