Chronic Ethanol Consumption and Generation of Etheno-DNA Adducts in Cancer-Prone Tissues

Adv Exp Med Biol. 2018;1032:81-92. doi: 10.1007/978-3-319-98788-0_6.


Chronic ethanol consumption is a risk factor for several human cancers. A variety of mechanisms may contribute to this carcinogenic effect of alcohol including oxidative stress with the generation of reactive oxygen species (ROS), formed via inflammatory pathways or as byproducts of ethanol oxidation through cytochrome P4502E1 (CYP2E1). ROS may lead to lipidperoxidation (LPO) resulting in LPO-products such as 4-hydoxynonenal (4-HNE) or malondialdehyde. These compounds can react with DNA bases forming mutagenic and carcinogenic etheno-DNA adducts. Etheno-DNA adducts are generated in the liver (HepG2) cells over-expressing CYP2E1 when incubated with ethanol;and are inhibited by chlormethiazole. In liver biopsies etheno-DNA adducts correlated significantly with CYP2E1. Such a correlation was also found in the esophageal- and colorectal mucosa of alcoholics. Etheno-DNA adducts also increased in liver biopsies from patients with non alcoholic steatohepatitis (NASH). In various animal models with fatty liver either induced by high fat diets or genetically modified such as in the obese Zucker rat, CYP2E1 is induced and paralleled by high levels of etheno DNA-adducts which may be modified by additional alcohol administration. As elevation of adduct levels in NASH children were already detected at a young age, these lesions may contribute to hepatocellular cancer development later in life. Together these data strongly implicate CYP2E1 as an important mediator for etheno-DNA adduct formation, and this detrimental DNA damage may act as a driving force for malignant disease progression.

Keywords: ALD; Colorectal Cancer; Cytochrome P4502E1; Esophageal Cancer; Etheno-DNA adducts; NASH; Reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Aldehydes / metabolism
  • Animals
  • Cytochrome P-450 CYP2E1 / metabolism*
  • DNA Adducts*
  • Ethanol / adverse effects
  • Fatty Liver / pathology
  • Humans
  • Lipid Peroxidation
  • Liver Neoplasms / pathology*
  • Malondialdehyde / metabolism
  • Rats
  • Rats, Zucker
  • Reactive Oxygen Species / metabolism


  • Aldehydes
  • DNA Adducts
  • Reactive Oxygen Species
  • Ethanol
  • Malondialdehyde
  • Cytochrome P-450 CYP2E1
  • 4-hydroxy-2-nonenal