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Supplement: International Research Conference on Food, Nutrition & Cancer

Phytoestrogens Regulate Vitamin D Metabolism in the Mouse Colon: Relevance for Colon Tumor Prevention and Therapy^{1 ,2}

Enikö Kállay, Herman Adlercreutz, Hesso Farhan, Daniel Lechner, Erika Bajna, Waltraud Gerdenitsch^*, Moray Campbell^** and Heide S. Cross³

Department of Pathophysiology and ^* Centre for Laboratory Animal Care, University of Vienna Medical School, Vienna, Austria, Institute for Preventive Medicine, Nutrition and Cancer, Folkhälsan Research Center and Division of Clinical Chemistry, FIN-00014, University of Helsinki, Helsinki, Finland and ^** Division of Medical Sciences, University of Birmingham Medical School, Birmingham, England

³To whom correspondence should be addressed. E-mail: heide.cross{at}akh-wien.ac.at.

Soybean products are highly represented in the traditional Asian diet. Major components of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of prostate and mammary tumors and possibly also of colon cancer in countries such as China and Japan. Serum 1,25-dihydroxyvitamin D₃ level is inversely related to incidence of some cancers. Levels are determined by skin exposure to ultraviolet light or, to a minor extent, nutritional uptake and by subsequent conversion of the precursor vitamin D to the active hormone by the cytochrome P450 hydroxylases CYP27A1, CYP27B1 (responsible for synthesis) and CYP24 (responsible for catabolism) in liver and kidney. However, vitamin D synthesis is also found in colonocytes and is enhanced during incipient malignancy. This may indicate an autocrine/paracrine role for this differentiation-inducing hormone in defense against progression. We were able to demonstrate that either a single large oral dose of genistein or feeding soy protein for 4 mo elevated CYP27B1 and decreased CYP24 expression in the mouse colon. Our data therefore suggest that an inverse correlation of soy product consumption with colon tumor incidence may be consequent to enhanced colonic synthesis of the antimitotic hormone 1,25-dihydroxyvitamin D₃.

KEY WORDS: • soy protein feeding • genistein • 1,25-dihydroxyvitamin D₃ synthesis • 25-hydroxyvitamin D₃-1-hydroxylase (CYP27B1) • 25-hydroxyvitamin D₃-24-hydroxylase (CYP24)

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