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Contributing Roles of CYP2E1 and Other Cytochrome P450 Isoforms in Alcohol-Related Tissue Injury and Carcinogenesis

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Human Cell Transformation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1164))

Abstract

The purpose of this review is to briefly summarize the roles of alcohol (ethanol) and related compounds in promoting cancer and inflammatory injury in many tissues. Long-term chronic heavy alcohol exposure is known to increase the chances of inflammation, oxidative DNA damage, and cancer development in many organs. The rates of alcohol-mediated organ damage and cancer risks are significantly elevated in the presence of co-morbidity factors such as poor nutrition, unhealthy diets, smoking, infection with bacteria or viruses, and exposure to pro-carcinogens. Chronic ingestion of alcohol and its metabolite acetaldehyde may initiate and/or promote the development of cancer in the liver, oral cavity, esophagus, stomach, gastrointestinal tract, pancreas, prostate, and female breast. In this chapter, we summarize the important roles of ethanol/acetaldehyde in promoting inflammatory injury and carcinogenesis in several tissues. We also review the updated roles of the ethanol-inducible cytochrome P450-2E1 (CYP2E1) and other cytochrome P450 isozymes in the metabolism of various potentially toxic substrates, and consequent toxicities, including carcinogenesis in different tissues. We also briefly describe the potential implications of endogenous ethanol produced by gut bacteria, as frequently observed in the experimental models and patients of nonalcoholic fatty liver disease, in promoting DNA mutation and cancer development in the liver and other tissues, including the gastrointestinal tract.

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Authors and Affiliations

  1. Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA

    Byoung-Joon Song, Mohamed A. Abdelmegeed & Young-Eun Cho

  2. Department of Food Science and Nutrition, Andong National University, Andong, Republic of Korea

    Young-Eun Cho

  3. Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA

    Mohammed Akbar

  4. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Johng S. Rhim

  5. Investigational Drug Branch, National Cancer Institute, NIH, Bethesda, MD, USA

    Min-Kyung Song

  6. Biochemistry and Molecular Pathology in the Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA

    James P. Hardwick

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  3. Young-Eun Cho
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  4. Mohammed Akbar
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Correspondence to Byoung-Joon Song .

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  1. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Johng S. Rhim

  2. Georgetown University Medical Center, Washington, DC, USA

    Anatoly Dritschilo

  3. Department of Medicine, McGill University Health Centre, Montréal, QC, Canada

    Richard Kremer

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Song, BJ. et al. (2019). Contributing Roles of CYP2E1 and Other Cytochrome P450 Isoforms in Alcohol-Related Tissue Injury and Carcinogenesis. In: Rhim, J., Dritschilo, A., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 1164. Springer, Cham. https://doi.org/10.1007/978-3-030-22254-3_6

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