Differential regulation of the dioxin-induced Cyp1a1 and Cyp1b1 genes in mouse hepatoma and fibroblast cell lines.

Toxicology Letters
Sudheer R BeedanagariOliver Hankinson

Abstract

The xenobiotic metabolizing enzymes Cyp1a1 and Cyp1b1 can be induced by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-rho-dioxin (dioxin) via the aryl hydrocarbon receptor (AhR). These genes are differentially induced by dioxin in different mouse cell lines. In the mouse hepatoma cell line Hepa1c1c7 (Hepa-1), the Cyp1a1 gene is induced to very high levels by dioxin, but the levels of Cyp1b1 mRNA are extremely low and are not inducible by dioxin. The reverse is the case for the mouse embryonic fibroblast cell line C3H10T1/2, in which Cyp1b1 is induced to very high levels by dioxin, but the levels of Cyp1a1 mRNA are extremely low and not inducible by dioxin. However, dioxin treatment leads to the recruitment of AhR to the enhancer regions of both genes in both cell lines. Somatic cell hybrid clones generated between the two cell lines display high levels of induction of both genes in response to dioxin. Strong reactivation of the Cyp1a1 gene was also observed in C3H10T1/2 cell line after treatment with the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine (5-AzadC) and the histone deacetylase inhibitor, trichostatin-A (TSA). However, only modest reactivation of Cyp1b1 was observed in Hepa-1 cells after 5-AzadC o...Continue Reading

Citations

Jul 16, 2010·Molecular Pharmacology·Sudheer R BeedanagariOliver Hankinson
Jan 1, 2012·Microbial Ecology in Health and Disease·Olav Albert Christophersen
Jun 17, 2015·Environmental Science and Pollution Research International·Petra BrenerováMiroslav Machala
Dec 14, 2011·The Biochemical Journal·Gráinne BarkessKatherine L West
Sep 23, 2014·Biological Trace Element Research·Marta Macedoni-LukšičJoško Osredkar
May 16, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Christopher D Sundberg, Oliver Hankinson
Aug 7, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Magnus Ingelman-SundbergYoichi Osawa
Jan 21, 2017·BioMed Research International·Rebeca Santes-PalaciosJesús Javier Espinosa-Aguirre
Nov 20, 2018·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Laurentius Ron Hoogenboom
Jun 20, 2019·International Journal of Molecular Sciences·Matti Viluksela, Raimo Pohjanvirta

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