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Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer

  • Claire Heit
  • Hongbin Dong
  • Ying Chen
  • Yatrik M. Shah
  • David C. Thompson
  • Vasilis Vasiliou
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Dextran Sulfate Sodium ADH1 Gene Ethanol Metabolism Alcohol Toxicity Ethanol Toxicity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Claire Heit
    • 1
  • Hongbin Dong
    • 1
  • Ying Chen
    • 1
  • Yatrik M. Shah
    • 2
  • David C. Thompson
    • 3
  • Vasilis Vasiliou
    • 4
  1. 1.Department of Pharmaceutical SciencesSchool of Pharmacy, University of Colorado Denver Anschutz Medical CampusAuroraUSA
  2. 2.Department of Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA
  3. 3.Department of Clinical PharmacySchool of Pharmacy, University of Colorado Anschutz Medical CampusAuroraUSA
  4. 4.Department of Environmental Health SciencesYale School of Public HealthNew HavenUSA

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