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Essential Nutrients in Carcinogenesis pp 253–267Cite as

Choline Deficiency and Chemical Carcinogenesis

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Abstract

We have reviewed the current status of our knowledge concerning the biologic effects of dietary choline (lipotrope) deficiency in modifying chemical carcinogenesis in experimental animals and discussed its possible mechanisms. Choline deficiency produces various pathologic lesions, involving virtually every organ of the body, as a result of a decrease in phospholipid and acetylcholine synthesis and in the supply of labile methyl groups. The liver is the only organ in which a relationship has been consistently demonstrated between choline deficiency and chemically induced tumors. The deficient diet enhances the initiating potency of several carcinogens and acts as a strong cocarcinogen. Diet also exerts a strong promoting effect, though the possibility that it is a complete carcinogen cannot be ruled out. Phase I enzymes of the carcinogen metabolizing system are uniformly depressed by choline deficiency, but very little information is available regarding the effects of diet on Phase II enzymes that detoxify carcinogen metabolites. Possible modifications of carcinogen-induced DNA damage and their repair processes have not been adequately scrutinized. Solid evidence suggests that feeding a choline-deficient diet leads to enhanced liver cell proliferation, an inadequate supply of methyl groups for transmethylation reactions, and membrane lipid peroxidation. Induced cell proliferation and hypomethylation of DNA may alter the state of gene expression, including that of specific cellular oncogenes. Lipid peroxidation may alter the structure and function of membrane receptors related to liver cell growth or may directly damage cellular DNA. Thus these alterations, individually or in combination, could play a critical role in the diet-induced modification of chemical carcinogenesis.

Supported by Grant CA-26556 from the National Cancer Institute, Department of Health and Human Services.

We gratefully acknowledge the preparation of the original manuscript by Ms. Nancy L. Cannon.

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Abbreviations

DEN:

diethylnitrosamine

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Authors and Affiliations

  1. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA

    Hisashi Shinozuka, Sikandar L. Katyal & Mohan I. R. Perera

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  1. Hisashi Shinozuka
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  2. Sikandar L. Katyal
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  3. Mohan I. R. Perera
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Editors and Affiliations

  1. Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland, USA

    Lionel A. Poirier

  2. Department of Pathology, Boston University School of Medicine, Boston, Massachusetts, USA

    Paul M. Newberne

  3. Food Research Institute, University of Wisconsin, Madison, Wisconsin, USA

    Michael W. Pariza

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Shinozuka, H., Katyal, S.L., Perera, M.I.R. (1986). Choline Deficiency and Chemical Carcinogenesis. In: Poirier, L.A., Newberne, P.M., Pariza, M.W. (eds) Essential Nutrients in Carcinogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1835-4_19

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