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Biological Basis of Alcohol-Induced Cancer pp 375–387Cite as

Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer

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

Abstract

Alcohol abuse leads to tissue damage including a variety of cancers; however, the molecular mechanisms by which this damage occurs remain to be fully understood. The primary enzymes involved in ethanol metabolism include alcohol dehydrogenase (ADH), cytochrome P450 isoform 2E1, (CYP2E1), catalase (CAT), and aldehyde dehydrogenases (ALDH). Genetic polymorphisms in human genes encoding these enzymes are associated with increased risks of alcohol-related tissue damage, as well as differences in alcohol consumption and dependence. Oxidative stress resulting from ethanol oxidation is one established pathogenic event in alcohol-induced toxicity. Ethanol metabolism generates free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has been associated with diminished glutathione (GSH) levels as well as changes in other antioxidant mechanisms. In addition, the formation of protein and DNA adducts associated with the accumulation of ethanol-derived aldehydes can adversely affect critical biological functions and thereby promote cellular and tissue pathology. Animal models have proven to be valuable tools for investigating mechanisms underlying pathogenesis caused by alcohol. In this review, we provide a brief discussion on several animal models with genetic defects in alcohol-metabolizing enzymes and GSH-synthesizing enzymes and their relevance to alcohol research.

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Acknowledgements

This work was supported in part by the National Institutes of Health Grants No. R24AA022057, No. R01EY14390, No. T32AA007464, CA148828, and DK095201.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, CO, 80045, USA

    Claire Heit, Hongbin Dong & Ying Chen

  2. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA

    Yatrik M. Shah

  3. Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA

    David C. Thompson

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

    Vasilis Vasiliou Ph.D.

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  1. Claire Heit
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  2. Hongbin Dong
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  3. Ying Chen
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  4. Yatrik M. Shah
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  5. David C. Thompson
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  6. Vasilis Vasiliou Ph.D.
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Correspondence to Vasilis Vasiliou Ph.D. .

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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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Heit, C., Dong, H., Chen, Y., Shah, Y.M., Thompson, D.C., Vasiliou, V. (2015). Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer. 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_22

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