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Vol. 26, Issue 4, 372-378, April 1998
Institute of Chemical Toxicology, Wayne State University
Cytochrome P450 2E1 (CYP2E1) and 2B (CYP2B) mRNA and protein
expression was examined in primary cultured rat hepatocytes under basal
cell culture conditions and in response to three prototypic CYP2E1
inducers, i.e. ethanol, acetone, and pyrazine. Xenobiotic treatment for 24 hr, initiated after hepatocytes had been maintained in
culture for 72 hr, resulted in 2-8-fold increases in CYP2E1 protein
levels, relative to untreated cells. A
2-fold increase in CYP2E1
protein levels was detected at the lowest concentration (1 mM) of each
of the xenobiotics examined. The increase in CYP2E1 protein expression
was not accompanied by any significant increase in 2E1 mRNA expression.
In contrast, CYP2B protein and mRNA levels were increased by acetone or
pyrazine at concentrations greater than 1 mM. Ethanol (up to 100 mM)
failed to significantly increase CYP2B protein or mRNA levels. The
maximal increases measured for CYP2B protein and mRNA (~25-fold and
~90-fold, respectively) after treatment of hepatocytes with acetone
were comparable to those measured in our laboratory, and reported by
others, for phenobarbital treatment of primary cultured rat
hepatocytes. The results of this study show that the pattern of
expression of CYP2E1 and 2B in this primary cultured rat hepatocyte
system and the magnitude of induction parallel those reported for rat
liver in vivo in response to these xenobiotics. This
primary hepatocyte culture system provides opportunities for studies of
the role of CYP2E1 in the metabolism and bioactivation of drugs,
chemicals, and putative carcinogens, as well as mechanistic studies on
xenobiotic-mediated regulation of CYP2E1 expression.
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