INDUCTION AND REGULATION OF CYP2E1 IN MURINE LIVER AFTER ACUTE AND CHRONIC ACETONE ADMINISTRATION

The effects of acute and chronic acetone administration on hepatic Cyp 2e1 were investigated in mice. Acute treatment consisted of a single d ose of acetone (5 ml/kg) given intragastrically, whereas the chronic r egimen consisted of 1% acetone in drinking water for 8 days. We examin ed 1) relative induction of Cyp2e1 protein by immunoblotting, 2) relat ive induction of enzyme catalytic activity (p-nitrophenol hydroxylatio n), and 3) Cyp2e1 mRNA levels associated with acute and chronic treatm ent regimens. Western immunoblotting, using a monoclonal antibody (Mab 1-98-1) specific for rat ethanol-inducible P-450, detected a band of M(r) 51,000 in liver microsomes of both control and acetone-treated mi ce. Densitometric quantitation showed significant enhancement of the i ntensity of this band by 4.4- and 5.3-fold after acute and chronic ace tone treatments, respectively. Hydroxylation of p-nitrophenol was incr eased 2.3-fold in microsomes from livers exposed acutely to acetone, a s compared with an increase of 3.7-fold in microsomes from livers expo sed chroni cally. The induction of Cyp2e1 protein, as well as of catal ytic activity, by acetone was not accompanied by significant alteratio ns in the levels of Cyp2e1 mRNA. These results demonstrate a differenc e in induced increases of Cyp2e1 between acute and chronic acetone tre atments: significantly higher induction of both protein and catalytic activity is induced by treatment under chronic vs. acute conditions.