Absence of a differential induction of cytochrome P450 2E1 by different alcoholic beverages in rats: implications for the aetiology of human oesophageal cancer.
Alcohol is an important risk factor for human oesophageal cancer. There is evidence from epidemiological studies that some specific alcoholic drinks, e.g. Calvados apple brandy, are associated with a greater risk than others. Alcohol induces cytochrome P450 2E1 (CYP2E1) and the hypothesis was tested that different alcoholic beverages, containing a variety of alcoholic compounds, could differentially induce expression of cytochrome P450 enzymes. Twelve groups of five rats each were treated for 3 days with different alcoholic beverages (ethanol alone, whisky, farm-produced or commercial Calvados brandy, beer, cider, wine) adjusted to 4, 10 or 20% of ethanol in drinking water. Immunoblotting using a monoclonal antibody specific for rat CYP2E1 revealed a single protein band in liver microsomes. Densitometric quantitation of microsomal proteins demonstrated a significant two-, three- and sixfold increase in band intensity after treatment with ethanol concentrations of 4, 10 and 20% respectively, compared to control rats drinking water alone. There was a dose-dependent increase in liver microsomal metabolism of CYP2E1 substrates (para-nitrophenol and dimethyl-nitrosamine) in ethanol-treated rats. However, there were no significant differences in the level of CYP2E1 protein or enzymatic activity between the different alcoholic beverages at the same ethanol concentration. There was a slight increase in hepatic CYP1A-related enzymatic activities in the alcohol-treated rats compared to the controls, but no difference between the treated groups either with dose of ethanol or type of beverage. These data show that induction of CYP2E1 with acute alcohol treatment is predominantly determined by the ethanol content of the beverage.
Lechevrel
M
M
Unit of Environmental Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
Wild
C P
CP
D000434:Alcoholic Beverages; D000818:Animals; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D007202:Indicators and Reagents; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1