Abstract. Obesity and elevated serum insulin growth factor-1 (IGF-1) level are major risk factors in the development of breast cancer. We investigated the long-term effects of highisoflavone soy intake and obesity on 7,12-dimethylbenz(a) anthracene (DMBA)-induced mammary tumor development and on serum IGF-1 and binding protein (IGFBP-3) levels. Lean and obese female Zucker rats fed casein or highisoflavone soy protein were orally gavaged at age 50 days with DMBA and sacrificed after 147 days. The majority of lean casein-fed rats (69%) developed mammary tumors compared to 50% in lean soy-fed rats (P=0.176). In the obese groups, 76% of soy-fed rats developed mammary tumors compared to 15% of obese casein-fed rats (P<0.001). At age 43 days, IGFBP-3 was increased in the lean soy-fed rats compared to the lean casein-fed rats (P<0.05). At age 99 days, soy-and obese casein-fed rats exhibited increased serum IGF-1 compared to the lean rats and this increase was maintained for the rest of the experiment (P<0.05). Obese rats fed casein exhibited increased IGFBP-3 levels (P<0.001). However, obese rats fed soy exhibited a significant decrease in IGFBP-3 levels compared to the lean soy-fed rats (P<0.001) and a significant decrease in IGFBP-3 levels compared to the obese casein-fed rats (P<0.001). At age 197 days, IGFBP-3 levels were increased in obese casein-and soy-fed rats (P<0.001). The results suggest that female Zucker rats fed casein diets are protected against DMBA-induced mammary tumors, which is not the case for those on high-isoflavone soy diet, and changes in the concentration of serum IGFBP-3 may contribute to the incidence of DMBA-induced mammary tumors.

Abstract. Obesity has been epidemic in the US for over two decades; almost 65% of adults in the US are overweight. Obesity has been linked with the risk of development of various cancers, including breast cancer. Dehydroepiandrosterone (DHEA) is an over-the-counter dietary supplement used as an immunomodulating, anti-depressant, anti-aging, anti-cardiovascular disease, and anti-cancer agent and antiobesity supplement. The objectives of this study were to investigate the long-term effects of obesity and DHEA treatment on body weight gain and on 7,12-dimethylbenz(a)-anthracene (DMBA)-induced mammary tumor development. Forty-three six-week-old obese female Zucker rats were used. Rats were randomly assigned and had ad libitum access to water and a diet of either chow (2016) as a control diet or chow with the addition of DHEA at a concentration of 6 g/kg of chow as a DHEA diet. All rats were orally gavaged at age 50 days with 65 mg DMBA/kg body weight. Rats were weighed and palpated twice weekly for detection of mammary tumors and sacrificed 155 days post-DMBA treatment. Obese rats fed the DHEA diet gained significantly less weight than obese control diet rats (P<0.001). At the end of the experiment, 55% of the control diet group developed mammary tumors, while no tumors were detected in the DHEA diet group (P<0.001). Our results suggest that DHEA treatment can reduce body weight gain and protects against DMBA-induced mammary tumor development in the obese Zucker rat model.

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