Methyl Insufficiency in Carcinogenesis

  • Lionel A. Poirier


In 1946 Copeland and Salmon found that the chronic administration of a choline-deficient diet to rats led to the formation of liver cancer1. Thus began one of the most prolonged and controversial areas of study in the field of chemical carcinogenesis. At first, such results were not regarded as surprising, for at the time other dietary deficiencies had also been shown to enhance carcinogenesis2,3. However, subsequent studies showed that the peanut meal diets used to obtain the choline deficiency were in fact contaminated with aflatoxin and that the original strain of rats used by Salmon’s group appeared to undergo genetic drift such that the original results in tumor formation by choline deficiency alone could no longer be repeated4–6. Although the original observations became doubted, they did serve to focus interests of other groups on the possible role of labile methyl group deficiency in carcinogenesis. Thus, Farber et al.7 showed that ethionine, an antagonist of the labile methyl group donor methionine also caused liver cancer in rats. Together, methionine and choline constitute the chief dietary sources of methyl groups. The Millers2 postulated that a labile methyl group insufficiency might by involved in hepatocarcinogenesis by the monomethyl aminoazo dyes. However, from 1960 to 1975, with the exception of the group of P. Newberne6, little research was conducted on the possible etiological role of dietary methyl donors in carcinogenesis. In the early 1970s, this group showed that several biochemical effects of hepatocarcinogens could be enhanced by the administration of diets marginally deficient in lipotropes, including methionine and choline8. Also, in the late 1970s, the group of Lombardi and Shinozuka showed that choline-devoid diets enhanced the activities of several hepatocarcinogens9–11 (Table 1).


Methyl Donor Chemical Carcinogenesis Peanut Meal B6C3F1 Mouse Choline Deficiency 
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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Lionel A. Poirier
    • 1
  1. 1.Division of Comparative ToxicologyNational Center for Toxicological ResearchJeffersonUSA

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