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

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|? 1.5, P1(t)? 0.9999) by TCDD, ?NF, PCB126, and ICZ, respectively. Only ?35% 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, ? 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.

SUBMITTER: Nault R 

PROVIDER: S-EPMC4096832 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature