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Carcinogenesis, Vol. 21, No. 5, 937-941, May 2000
© 2000 Oxford University Press


Molecular Epidemiology and Cancer Prevention

Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones

Toshihisa Ohta1,2, Seiichi Nakatsugi1, Kouji Watanabe1, Toshihiko Kawamori1, Fumiyasu Ishikawa2, Masami Morotomi2, Shigeyuki Sugie3, Toshiya Toda4, Takashi Sugimura1 and Keiji Wakabayashi1,5

1 Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
2 Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-shi, Tokyo 186-8650,
3 Gifu University School of Medicine, 40 Tsukasa-machi, Gifu-shi, Gifu 500-8705,
4 Fujicco Co. Ltd, 6-13-4 Minatojimanakamachi, Chuo-ku, Kobe, Hyogo, 650-8558, Japan

High consumption of soybean and soybean-related products is hypothesized to contribute to protection against breast cancer. Soybean is a rich source of genistein, a putative cancer chemopreventive agent. Fermented soy milk (FSM), which is made of soy milk fermented with the Bifidobacterium breve strain Yakult, contains larger amounts of the isoflavone aglycones genistein and daidzein than unfermented soy milk. In the present study, we examined the effects of FSM and its component isoflavone mixture (genistein:daidzein 4:1) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in rats. Starting at 7 weeks of age, female Sprague–Dawley rats were given PhIP at a dose of 85 mg/kg body wt by intragastric administration four times a week for 2 weeks. They were fed control high fat basal diet or experimental high fat diet containing 10% FSM or 0.02 or 0.04% isoflavone mixture during and after carcinogen exposure. The incidences (percentage of rats with tumors) of mammary gland tumors were 71% in the control diet group, 51% in the FSM group and 68 and 61% in the groups treated with isoflavone mixture at 0.02 and 0.04%, respectively. Mammary tumor multiplicities (number of tumors per rat) were 1.2 ± 0.2 for 10% FSM, 2.2 ± 0.4 for 0.02% isoflavone mixture and 1.5 ± 0.3 for 0.04% isoflavone mixture, being clearly smaller than the control diet value (2.6 ± 0.5). Furthermore, feeding of FSM and the isoflavone mixture at both doses reduced the sizes of mammary tumors. Since the amounts of isoflavones in 10% FSM are approximately equivalent to those in the 0.02% isoflavone mixture, the chemopreventive activity of FSM could be partly attributable to the presence of isoflavones such as genistein and daidzein.


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