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Alcohol and Cancer pp 203–221Cite as

Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1032))

Abstract

Excessive consumption of alcohol is a leading cause of lifestyle-induced morbidity and mortality worldwide. Although long-term alcohol abuse has been shown to be detrimental to the liver, brain and many other organs, our understanding of the exact molecular mechanisms by which this occurs is still limited. In tissues, ethanol is metabolized to acetaldehyde (mainly by alcohol dehydrogenase and cytochrome p450 2E1) and subsequently to acetic acid by aldehyde dehydrogenases. Intracellular generation of free radicals and depletion of the antioxidant glutathione (GSH) are believed to be key steps involved in the cellular pathogenic events caused by ethanol. With continued excessive alcohol consumption, further tissue damage can result from the production of cellular protein and DNA adducts caused by accumulating ethanol-derived aldehydes. Much of our understanding about the pathophysiological consequences of ethanol metabolism comes from genetically-engineered mouse models of ethanol-induced tissue injury. In this review, we provide an update on the current understanding of important mouse models in which ethanol-metabolizing and GSH-synthesizing enzymes have been manipulated to investigate alcohol-induced disease.

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Acknowledgements

This work was supported in part by the National Institutes of Health Grants.

AA022057 (VV), AA017754 (VV), EY017963 (VV), EY11490 (VV), AA025093 (YC), and AA023699 (SMM).

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Authors and Affiliations

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

    Stephanie Marshall, Ying Chen, Surendra Singh, Pablo Berrios-Carcamo, Nicholas Apostolopoulos, Jaya Prakash Golla & Vasilis Vasiliou

  2. Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile

    Pablo Berrios-Carcamo

  3. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado, Aurora, CO, USA

    Claire Heit

  4. Department of Clinical Pharmacy, Skaggs School of Pharmacy, University of Colorado, Aurora, CO, USA

    David C. Thompson

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Correspondence to Vasilis Vasiliou .

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Editors and Affiliations

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

    Vasilis Vasiliou

  2. Distilled Spirits Council of the US, Washington, DC, USA

    Samir Zakhari

  3. Mishra Laboratory, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Lopa Mishra

  4. Salem Medical Centre, University of Heidelberg, Heidelberg, Baden-Württemberg, Germany

    Helmut K. Seitz

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Marshall, S. et al. (2018). Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer. In: Vasiliou, V., Zakhari, S., Mishra, L., Seitz, H. (eds) Alcohol and Cancer. Advances in Experimental Medicine and Biology, vol 1032. Springer, Cham. https://doi.org/10.1007/978-3-319-98788-0_14

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