... citation for the above?

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression
of critical genes associated with cholesterol metabolism, bile acid
biosynthesis, and bile transport in rat liver: a microarray study.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatotoxin
that exerts its toxicity through binding to the aryl hydrocarbon
receptor (AhR) and the subsequent induction or repression of gene
transcription. In order to further identify novel genes and pathways
that may be associated with TCDD-induced hepatotoxicity, we
investigated gene changes in rat liver following exposure to single
oral doses of TCDD. Male Sprague-Dawley rats were administered single
doses of 0.4 microg/kg bw or 40 microg/kg bw TCDD and killed at 6 h,
24 h, or 7 days, for global analyses of gene expression. In general,
low-dose TCDD exposure resulted in greater than 2-fold induction of
genes coding for a battery of phase I and phase II metabolizing
enzymes including CYP1A1, CYP1A2, NADPH quinone oxidoreductase,
UGT1A6/7, and metallothionein 1. However, 0.4 microg/kg bw TCDD also
altered the expression of Gadd45a and Cyclin D1, suggesting that even
low-dose TCDD exposure can alter the expression of genes indicative of
cellular stress or DNA damage and associated with cell cycle control.
At the high-dose, widespread changes were observed for genes encoding
cellular signaling proteins, cellular adhesion, cytoskeletal and
membrane transport proteins as well as transcripts coding for lipid,
carbohydrate and nitrogen metabolism. In addition, decreased
expression of cytochrome P450 7A1, short heterodimer partner (SHP;
gene designation nr0b2), farnesyl X receptor (FXR), Ntcp, and Slc21a5
(oatp2) were observed and confirmed by RT-PCR analyses in independent
rat liver samples. Altered expression of these genes implies major
deregulation of cholesterol metabolism and bile acid synthesis and
transport. We suggest that these early and novel changes have the
potential to contribute significantly to TCDD induced hepatotoxicity
and hypercholesterolemia. PMID: 16054898