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The Role of Oxidative Stress in Hepatocarcinogenesis

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Book cover Studies on Hepatic Disorders

Abstract

Various mechanisms contribute to ethanol-mediated hepatocarcinogenesis including the development of hepatic cirrhosis, oxidative stress, the action of acetaldehyde, the first oxidative metabolite of ethanol oxidation with its effect on the antioxidative defense and DNA repair systems and on epigenetics, additional epigenic alterations due to effects of ethanol on DNA/histone acetylation and deacetylation, the reduction of retinol and retinoic acid associated with hyperproliferation and the loss of cell differentiation, changes in intercellular signal transduction pathways, and immunosuppression. Reactive oxygen species (ROS) can be produced through a number of enzymatic and non-enzymatic reactions resulting finally in DNA damage. Cytochrome P-4502E1 induced by chronic ethanol consumption generates ROS with oxidative DNA damage and lipid peroxidation. Lipid peroxidation products such as 4-hydroxynonenal bind to DNA and create highly carcinogenic etheno DNA adducts. Oxidative stress may be indirectly enhanced by acetaldehyde and by an ethanol-mediated loss of retinol and retinoic acid. Finally, hepatic iron contributes to oxidative stress. Chronic ethanol intake increases liver iron by changing the regulation of its retention and uptake.

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Authors and Affiliations

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

    Helmut K. Seitz M.D. & Sebastian Mueller

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  1. Helmut K. Seitz M.D.
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  2. Sebastian Mueller
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Correspondence to Helmut K. Seitz M.D. .

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  1. Department of Health Sciences, University of Eastern Piedmont Amedeo Avogadro, Novara, Italy

    Emanuele Albano

  2. Department of Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, School of Medicine, University of Torino, Torino, Italy

    Maurizio Parola

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Seitz, H.K., Mueller, S. (2015). The Role of Oxidative Stress in Hepatocarcinogenesis. In: Albano, E., Parola, M. (eds) Studies on Hepatic Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-15539-5_21

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