Ethanol-induced cytochrome P450 2E1 causes carcinogenic etheno-DNA lesions in alcoholic liver disease

Aims: Oxidative stress is thought to play a major role in the pathogenesis of hepatocellular cancer (HCC), the most frequent complication of alcoholic liver disease (ALD). However, its underlying mechanisms are poorly understood. In hepatocytes of patients with ALD, we could recently detect significant levels of carcinogenic exocyclic etheno-DNA adducts that are formed by the reaction of the lipid peroxidation product 4-hydroxynonenal (4-HNE) with nucleobases. Methods and results: We here show in patients with ALD that 4-HNE and exocyclic etheno-DNA adducts closely correlate with the expression of CYP2E1 express…