Assessment of interactions of diverse ternary mixtures in an estrogen receptor-alpha reporter assay

Toxicology and Applied Pharmacology
G D CharlesEdward W Carney

Abstract

This study used an MCF-7 cell based ER-alpha reporter gene assay to assess chemical interactions within the following ternary mixtures: (1) three synthetic pesticides, methoxychlor (MXC), o,p-DDT, and dieldrin; (2) three polyaromatic hydrocarbons, benzo[a]pyrene (BAP), 1,2-benzanthracene (BENZ), and chrysene (CHRY); and (3) an endogenous estrogen, [17beta-estradiol, (E(2))]; a phytoestrogen, genistein (GEN); and a synthetic estrogen, o,p-DDT. A full factorial design in which four concentrations of each chemical were assessed in all possible combinations (64 treatment groups) was utilized. In addition, mixtures were tested in both a low range (concentrations near the individual chemical response thresholds) and a high range ( approximately 2-10x higher) experiment. A response surface was estimated using a nonlinear mixed model, and the cumulative response in each mixture was evaluated for departure from additivity. The mixture of E(2), GEN, and DDT exhibited antagonistic interactions (p < 0.001) in both concentration ranges. However, specific interactions between E(2)/GEN and E(2)/DDT differed between the low and high range concentrations. The BAP/BENZ/CHRY mixture did not depart significantly from additivity (p = 0.66) in eithe...Continue Reading

Citations

Sep 18, 2003·Food Additives and Contaminants·C TarrafR Talhouk
May 6, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·George P DastonRobert J Kavlock
May 13, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Elisabete SilvaAndreas Kortenkamp
Jan 5, 2008·Environmental Health Perspectives·Andreas Kortenkamp
Oct 21, 2017·Toxics·Edna RibeiroSusana Viegas
Jun 23, 2018·The Science of the Total Environment·Muhammad Arslan Kamal HashmiWerner Brack
May 31, 2011·Regulatory Toxicology and Pharmacology : RTP·Susanne N KolleBennard van Ravenzwaay

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