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United States Department of Agriculture

Agricultural Research Service

Title: Enhanced Estrogenic Responses and Sensitivity to Azosymethane Following Dietary Soy Isoflavone Supplementation in Older Female Rats

Authors
item Daly, K - UNIV MD, COLLEGE PARK
item Tracy, A - UNIV MD, COLLEGE PARK
item Malik, M - USUHS, BETHESDA, MD
item Wang, Thomas
item Francke-Carroll, S - CFSAN,FDA,COLLEGE PK,MD
item Magnusen, B - UNIV MD, COLLEGE PARK

Submitted to: Food and Chemical Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 1, 2006
Publication Date: April 1, 2007
Citation: Daly, K.T., Tracy, A.C., Malik, M., Wang, T.T., Francke-Carroll, S., Magnuson, B.A. 2007. Enhanced estrogenic responses and sensitivity to azosymethane following dietary soy isoflavone supplementation in older female rats. Food and Chemical Toxicology. 45(4):628-637.

Interpretive Summary: Soy isoflavones are becoming popular supplements among middle-aged women based on their potential for protection against cancer and their use as alternative hormone replacement therapy. In the present study, we investigated the effects of dietary soy isoflavones and age on early stage colon cancer in an azoxymethane (AOM)–induced colon cancer model in female rats. Young, mature, and old female Fisher 344 rats were fed either the control diet or a diet containing 0.4% isoflavone supplement for 1 week, injected once with 20 mg/kg azoxymethane (AOM) and maintained on these diets for another 12 weeks. The development of aberrant crypt foci was reduced in older rats, but not by the soy-isoflavone diet. Colonic crypt density significantly decreased with age and was further reduced in rats fed the soy supplement. Uterine weights, serum estradiol, and serum isoflavone levels were increased in mature and old female rats fed the soy-supplemented diets compared to age-matched controls, suggesting an increasing estrogenic response with age to isoflavone supplementation. Isoflavone-supplemented rats had greater weight loss and a slower recovery following the AOM injection compared to rats fed the control diet and these changes increased with age. Five of the 21 rats fed the isoflavone-supplement died before the end of the experiment while all animals on the control diet survived to term. The unexpected adverse effects of soy isoflavones in aged female animals needs further examination because women, and particularly older women, are the prime target population for consumption of soy supplements. This work provides novel biological as well as safety information on soy supplement in females which will benefit basic, as well as applied, nutrition research on the biology and safety of food supplement.

Technical Abstract: Soy isoflavones are becoming popular supplements among middle-aged women based on their potential protection against cancer and their use as alternative hormone replacement therapy. We investigated the effects of dietary soy isoflavones and age on early stage colon cancer in female rats. Young, mature, and old female Fisher 344 rats were fed either the control diet or a diet containing 0.4% isoflavone supplement for 1 week, injected once with 20 mg/kg azoxymethane (AOM) and maintained on the diets for another 12 weeks. Isoflavone-supplemented rats had greater weight loss and a slower recovery following the AOM injection compared to rats fed the control diet and these changes increased with age. Five of the 21 rats fed the isoflavone-supplement died before the end of the experiment while all animals on the control diet survived to term. The development of aberrant crypt foci was reduced in older rats, but not by the soy-isoflavone diet. Colonic crypt density significantly decreased with age and was further reduced in rats fed the soy supplement. Uterine weights, serum estradiol and serum isoflavone levels were increased in mature and old female rats fed the soy-supplemented diets compared to age-matched controls, suggesting an increasing estrogenic response with age to isoflavone supplementation. The adverse effects of soy isoflavones in aged female animals need further examination because women, and particularly older women, are the prime target population for consumption of soy supplements.

Last Modified: 10/25/2014
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