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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Comparisons of differential gene expression elicited by TCDD, PCB126, *NF, or ICZ in mouse hepatoma Hepa1c1c7 cells and C57BL/6 mouse liver.

Authors: Nault, Rance; Forgacs, Agnes L; Dere, Edward; Zacharewski, Timothy R

Published In Toxicol Lett, (2013 Oct 23)

Abstract: The aryl hydrocarbon receptor (AhR) is a promiscuous receptor activated by structurally diverse synthetic and natural compounds. AhR activation may lead to ligand-specific changes in gene expression despite similarities in mode of action. Therefore, differential gene expression elicited by four structurally diverse, high affinity AhR ligands (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10nM, 30 *g/kg), 3,3',4,4',5-pentachlorobiphenyl (PCB126; 100nM, 300*g/kg), *-naphthoflavone (*NF; 10 *M, 90 mg/kg), and indolo[3,2-b]carbazole (ICZ; 1*M)) in mouse Hepa1c1c7 hepatoma cells and C57BL/6 mouse liver samples were compared. A total of 288, 183, 119, and 131 Hepa1c1c7 genes were differentially expressed (|fold-change|ýýý 1.5, P1(t)ýýý 0.9999) by TCDD, *NF, PCB126, and ICZ, respectively. Only ýýý35% were differentially expressed by all 4 ligands in Hepa1c1c7 cells. In vivo, 661, 479, and 265 hepatic genes were differentially expressed following treatment with TCDD, *NF, and PCB126, respectively. Similar to Hepa1c1c7 cells, ýýý 34% of gene expression changes were common across all ligands. Principal components analysis identified time-dependent gene expression divergence. Comparisons of ligand-elicited expression between Hepa1c1c7 cells and mouse liver identified only 11 common gene expression changes across all ligands. Although metabolism may explain some ligand-specific gene expression changes, PCB126, *NF, and ICZ also elicited divergent expression compared to TCDD, suggestive of selective AhR modulation.

PubMed ID: 23994337 Exiting the NIEHS site

MeSH Terms: Animals; Carbazoles/toxicity*; Cell Line, Tumor; Female; Gene Expression Profiling/methods; Gene Expression/drug effects; Liver Neoplasms, Experimental/genetics; Liver Neoplasms, Experimental/metabolism; Liver/drug effects*; Liver/metabolism; Liver/physiology; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Polychlorinated Biphenyls/toxicity*; Receptors, Aryl Hydrocarbon/biosynthesis*; Receptors, Aryl Hydrocarbon/genetics; Tetrachlorodibenzodioxin/toxicity*; beta-Naphthoflavone/toxicity*

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