EFFECT OF LONG-TERM ETHANOL PRETREATMENT ON THE METABOLISM OF DICHLOROMETHANE TO CARBON-MONOXIDE IN RATS

The present study investigates the influence of long-term ethanol (ETO H) treatment of rats [10% (v/v) for 4, 12, and 36 weeks] on the metabo lism of DCM after its oral and inhalative uptake to CO. Biotransformat ion of DCM to CO as measured by carboxyhemoglobin (COHb) formation was stimulated after long-term ETOH treatment in rats. A single oral dose of DCM (6.2 mmol/kg body mass) caused a significant increase of COHb, the maximum of about 9% occurring approximately 6 hr after DCM admini stration. In comparison to this control, in the blood of rats pretreat ed with ETOH (10% v/v) for 4, 12, and 36 weeks COHb values of 18, 17, and 13%, respectively, were measured. Long-term ETOH treatment followe d by inhalation of 100, 500, and 2500 ppm DCM for 4 hr stimulated the formation of COHb, compared to controls. The elevation of COHb level w as accompanied by decreased concentrations of DCM in the blood. The re ason for the elevated biotransformation of DCM was ascertained by mean s of the determination of p-nitrophenol and aniline hydroxylation in l iver microsomes of rats after long-term ETOH treatment to be an increa se in cytochrome P450-dependent enzyme activities. (C) 1997 Academic P ress.