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The effect of synthetic glucocorticoid, dexamethasone on CYP1A1 inducibility in adult rat and human hepatocytes
Authors:Monostory Katalin  Kohalmy Krisztina  Prough Russell A  Kóbori László  Vereczkey László
Affiliation:Chemical Research Center, Hungarian Academy of Sciences, PO Box 17, H-1525 Budapest, Hungary. monostor@chemres.hu
Abstract:Glucocorticoids act synergistically with polycyclic aromatic hydrocarbons in increasing mRNA and protein levels of CYP1A1 in rat liver. The action of dexamethasone to modify CYP1A1 expression has been investigated in adult human hepatocytes. The effect of dexamethasone on the induction of CYP1A1 by 3-methylcholanthrene is different in rat and human liver cells. Dexamethasone potentiates the induction of CYP1A1 about 3- to 4-fold in rat cells. In human hepatocytes, it reduces CYP1A1 induction by 50-60% at enzyme protein level, while it does not have an effect on CYP1A1 mRNA amount.
Keywords:AhR, arylhydrocarbon receptor   GR, glucocorticoid receptor   GRE, glucocorticoid responsive element   HBSS, Hank’s balanced salt solution   PAH, polycyclic aromatic hydrocarbon   P450, cytochrome P450
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