Mechanisms of Dietary Modification of Aflatoxin B1 Carcinogenesis

  • George Bailey
  • Matthew Taylor
  • Daniel Selivonchick
  • Thomas Eisele
  • Jerry Hendricks
  • Joseph Nixon
  • Norman Pawlowski
  • Russell Sinnhuber
Part of the Basic Life Sciences book series (volume 6)


Trout were fed a range of dietary components which altered their carcinogenic response to aflatoxin B1 (AFB1). Dietary protein at levels substantially exceeding nutritional requirements were synergistic with AFB1. Cyclopropene fatty acids (CPFA) were carcinogenic when fed alone at 20 or 55 ppm, and synergistic when fed with AFB1 In contrast, several flavonoid and indole compounds, especially β-naphthoflavone (β-NF) and indole-3-carbinol, Inhibited the carcinogenic response when fed prior to and along with AFB1.

The mechanisms by which some of these dietary factors modulate AFB1 carcinogenesis were investigated. Dietary β-naphthoflavone was shown to substantially induce the levels of mixed function oxidase (MFO) activities assayed in vitro. These changes were accompanied by alterations in AFB1 metabolism and binding in freshly isolated hepatocytes. AFB1 incubated in hepatocytes freshly isolated from fish fed β-NF diet was metabolized more rapidly, showed enhanced rates of detoxication reactions, and decreased accumulation of AFB1-DNA adducts compared to control hepatocytes. These results suggest that β-NF inhibits AFB1 carcinogenesis at least in part by altering MFO activities such that detoxication is enhanced and initial DNA damage by AFB1 is reduced.

In contrast, high dietary protein is a synergist for AFB1 carcinogenesis, and this appears to occur primarily by enhancing the transformation probability for AFB1-initiated genome damage. Fish treated with AFB1 as embryos and then reared on high protein diets had substantially higher incidences of hepatocellular carcinoma (86%) than similarly treated fish fed normal protein diet (44%) or high protein controls without AFB1 exposure (0–2%).

The synergistic behavior of dietary CPFAs also appears to partially Involve enhanced transformation following DNA damage by AFB1. Fish exposed as embryos to AFB1 and then fed CPFA-containing diets are known to show promotion effects similar to the high protein results (Hendricks, J. D., Proc. 11th Int. Symp. of the Princess Takamatsu Cancer Research Fund, in press.)

However, factors other than promotion are involved in the synergism between CPFA and AFB1. Preliminary studies indicate that dietary CPFAs repress MFO activities and depress DNA damage by AFB1 in vitro. If this occurs in vivo, then the net synergistic effect of dietary CPFAs would involve depression of Initial AFB1-induced DNA damage, but highly efficient promotion of transformation from the remaining lesions.


Rainbow Trout Dietary Protein High Dietary Protein Mixed Function Oxidase Cyclopropene Fatty Acid 
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Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • George Bailey
    • 1
  • Matthew Taylor
    • 1
  • Daniel Selivonchick
    • 1
  • Thomas Eisele
    • 1
  • Jerry Hendricks
    • 1
  • Joseph Nixon
    • 1
  • Norman Pawlowski
    • 1
  • Russell Sinnhuber
    • 1
  1. 1.Department of Food Science and TechnologyOregon State UniversityCorvallisUSA

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