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Biological Basis of Alcohol-Induced Cancer pp 59–70Cite as

Alcohol and Cancer: An Overview with Special Emphasis on the Role of Acetaldehyde and Cytochrome P450 2E1

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 815))

Abstract

The mechanisms by which chronic alcohol consumption enhances carcinogenesis include acetaldehyde (AA) generated by alcohol dehydrogenase and reactive oxygen species (ROS) generated predominantly by cytochrome P450 2E1 (CYP2E1), but also by other factors during inflammation. In addition, ethanol also alters epigenetics by changing DNA and histone methylation and acetylation. A loss of retinoic acid due to a CYP2E1-related enhanced degradation results in enhanced cellular proliferation and decreased cell differentiation. Changes in cancer genes and in signaling pathways (MAPK, RAS, Rb, TGFβ, p53, PTEN, ECM, osteopontin, Wnt) may also contribute to ethanol-mediated mechanisms in carcinogenesis. Finally, immunosuppression may facilitate tumor spread. In the present review major emphasis is led on AA and ROS. While AA binds to proteins and DNA generating carcinogenic DNA adducts and inhibiting DNA repair and DNA methylation, ROS results in lipid peroxidation with the generation of lipid peroxidation products such as 4-hydoxynonenal which binds to DNA-forming highly carcinogenic exocyclic DNA adducts. ROS production correlates significantly with CYP2E1 in the liver but also in the esophagus, and its generation can be significantly reduced by the specific CYP2E1 inhibitor clomethiazole. Finally, CMZ also inhibits alcohol-mediated nitrosamine-induced hepatocarcinogenesis.

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Acknowledgment

Original studies were supported by the Dietmar Hopp and Manfred Lautenschläger Foundations.

Author information

Authors and Affiliations

  1. Centre of Alcohol Research, University of Heidelberg, Germany and Salem Medical Centre, Heidelberg, Germany

    Helmut K. Seitz M.D., A.G.A.F.

  2. Centre of Alcohol Research, University of Heidelberg AND Department of Medicine, Salem Medical Centre, Zeppelinstr. 11-33, 69121, Heidelberg, Germany

    Sebastian Mueller

Authors
  1. Helmut K. Seitz M.D., A.G.A.F.
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  2. Sebastian Mueller
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Corresponding author

Correspondence to Helmut K. Seitz M.D., A.G.A.F. .

Editor information

Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the United States, Washington, District of Columbia, USA

    Samir Zakhari

  3. Centre of Alcohol Research, University of Heidelberg, Germany and Salem Medical Centre, Heidelberg, Germany

    Helmut K. Seitz

  4. Department of Pathology, Anatomy, & Cell, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Jan B. Hoek

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© 2015 Springer International Publishing Switzerland

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Seitz, H.K., Mueller, S. (2015). Alcohol and Cancer: An Overview with Special Emphasis on the Role of Acetaldehyde and Cytochrome P450 2E1. In: Vasiliou, V., Zakhari, S., Seitz, H., Hoek, J. (eds) Biological Basis of Alcohol-Induced Cancer. Advances in Experimental Medicine and Biology, vol 815. Springer, Cham. https://doi.org/10.1007/978-3-319-09614-8_4

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