Fig. 1

Ethanol metabolism and its role in carcinogenesis. Ethanol is metabolised via alcohol dehydrogenase (ADH) and via cytochrome P4502E1 (CYP2E1) to acetaldehyde. Acetaldehyde is further metabolised via acetaldehyde dehydrogenase (ALDH) to untoxic acetate. ADH1B and ADH1C show polymorphism with different enzyme kinetics and thus different acetaldehyde production. ALDH2 is mutated in Asians resulting in low enzyme activity and accumulation of acetaldehyde. Acetaldehyde is toxic, mutagenic and carcinogenic, results in DNA adducts, inhibits DNA repair and DNA methylation and damages the antioxidative defense system (AODS). In addition, ethanol oxidation via CYP2E1 also generates reactive oxygene species (ROS) which cannot be sufficiently detoxified due to an injured AODS and thus results in DNA adducts. CYP2E1 also activates various procarcinogens to their ultimative carcinogenic metabolites and metabolises retinoic acid resulting in low levels of hepatic retinoic acid