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KO and Wild-Type Mice from Carcinogen-Induced Colon Cancer1,2
Department of Food Science, University of Missouri, Columbia MO 65211;
* Veterinary Medical Diagnostic Laboratory, University of Missouri, Columbia MO 65211;
Departments of Biochemistry, Animal Sciences and Child Health, University of Missouri, Columbia MO 65211;
** Department of Surgical Oncology, University of Illinois, Chicago, IL 60612; and
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224.
3 To whom correspondence should be addressed. E-mail: macdonaldr{at}missouri.edu.
Consumption of soy foods has been weakly associated with reduced colon cancer risk. Colon cancer risk is influenced by estrogen exposure, although the mechanism through which this occurs is not defined. Conversion of estradiol (E2) to estrone (E1) may be protective in the colon. We hypothesized that dietary phytoestrogens, or E1, would reduce colon tumorigenesis via an estrogen receptor (ER)-dependent mechanism. Ovariectomized ER
KO or wild-type (WT) female mice were fed diets containing casein (Casein), soy protein without isoflavones (Soy-IF), soy protein + genistein (Soy+Gen), soy protein + NovaSoy (Soy+NSoy) or soy protein + estrone (Soy+E1) from weaning. Colon tumors were induced with azoxymethane. Tumor incidence was affected by diet but not genotype. Colon tumor incidence was lower in ERKO and WT mice fed the Soy+E1 diet compared with those fed the casein or Soy-IF diets. Mice fed Soy+NSoy had a lower tumor incidence than mice fed casein, but not Soy-IF. Genistein did not affect tumor incidence. Soy protein, independently of phytoestrogens or E1, significantly reduced relative colon weight, tumor burden and multiplicity. Relative colon weight was lower (P = 0.008) in mice fed Soy+E1 than in the other soy-fed groups. Tumor incidence in this group was lower than in the casein and soy-IF–fed groups and tended to be lower than in the others (P = 0.020). Hence, soy protein and NSoy protect mice from colon cancer, and E1 further reduces colon tumorigenesis in mice, independently of ER.
KEY WORDS: • colon cancer • genistein • isoflavone • azoxymethane • estrone
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