Effects of Dietary Genistein on Hormone-Dependent Rat Mammary Carcinogenesis Induced by Ethyl Methanesulphonate

Abstract

Genistein, a major soy isoflavone having weak estrogenic activities, has been suggested to reduce the risk of breast cancer incidence. However, many studies have yielded inconsistent results. We investigated the effects of dietary genistein on the development of breast cancer using ethyl methanesulphonate (EMS) chemically induced rat model of hormone-dependent mammary carcinoma. Female Wistar King A rats were orally given EMS for 12 wk and fed isoflavone-free NIH-07PLD diets with or without genistein, beginning immediately after weaning period. All EMS-treated rats fed either diet developed estrogen and/or progesterone receptor-positive mammary carcinoma by 24 wk. The addition of either low or high genistein, which produced the plasma concentrations comparable with those observed in humans consuming high soy diets, did not show any preventive activity. Soy-containing pellet food, exhibiting substantial plasma concentrations of isoflavones such as genistein, daidzein, equol, and glycitein, significantly increased the latency periods, compared to either NIH-07PLD diet with low (P = 0.027) or high (P = 0.034) genistein. Body weights, total EMS uptakes, and urinary estradiol concentrations were not significantly different among groups. These data indicate that genistein does not exert clear preventive effects and that isoflavone components other than genistein might be preventive against hormone-dependent mammary carcinogenesis.

ACKNOWLEDGMENTS

We wish to thank Y. Tanaka, Animal Center of Nakamura Gakuen University, for help in conducting animal experiments. This work was supported by the Grant-in-Aid for Scientific Research C (20500734) and the Strategic Research Foundation Grant-aided Project for Private Universities 2010–2012 (S1002011) from the Ministry of Education, Culture, Sports, Science & Technology in Japan, and the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan

Notes

The composition of modified NIH-07PLD diet is as follows (per kg diet): 140 g white fish meal, 80 g gluten meal, 285 g ground corn, 406 g wheat flour, 20 g Brewer's yeast, 25 g corn oil, 7.5 g molasses, 36.3 g vitamin and mineral mix. In Foonote 1, correct to add “g” after “36.3”? Vitamins and trace elements are as follows (per kg diet): 3.2 mg CuSO₄, 88 mg FeSO₄, 149 mg MnSO₄, 25 mg ZnCO₃, 1.6 mg Ca(IO₃)₂, 11 mg vitamin B₁, 4.7 mg vitamin B₂, 1.9 mg vitamin B₆, 44 mg vitamin E, in addition to 5 μg MeHg/g. The proximate composition of the diet is as follows: 25.4% crude protein, 6.8% crude fat, 2.0% crude fiber, 6.6% crude ash, 51.6% nitrogen-free extract, 369 kcal/100 g total calories.