| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Recently, the incidence of endometrial carcinoma has been increasing in Japan as well as in the Western countries. Epidemiological studies gave suggested that consumption of diets containing soybeans and soy-based products reduce the risk of endometrial cancers. However, the effects of isoflavones on endometrial carcinogenesis have not been reported. Thus, we have attempted to address whether genistein and didzein exert suppressive effects on mouse endometrial carcinogenesis.
Short-term experiment : Single s.c. administration of genistein (1 mg/30 g bw) significantly decreased the levels of E2 (5 ppm)-induced expression of c-jun, IL-1α and TNF-a mRNAs in the uteri of ovarectomized mice (P<0.005, P<0.05 and P<0.01, respectively). Daidzein significantly inhibited E2-induced expression of c-fos and IL-1α (P<0.01).
Long-term experiment (30 weeks) : 140 female ICR mice were given N-methyl-N-nitrosourea containing solution (1 mg/100 g bw) and normal saline (as controls) into the left and right uterine corpora, respectively. They were divided into six groups ; group 1 was given E2 (5 ppm) alone. Group 2 was given E2 and genistein (1 mg/30 g bw, s.c., every 4 weeks). Group 3 was exposed to E2 and daidzein (1 mg/30 g bw, s.c., every 4 weeks). Groups 4 and 5 respectively received genistein and daidzein, and were kept on the basal diet. Group 6 was kept on the basal diet and served as a control. At the termination of the experiment, incidences of endometrial adenocarcinoma and atypical hyperplasia of the group given E2 and genistein or daidzein were significantly lower than the group given E2 alone (P<0.01 and P<0.05, respectively). It is suggested that both gensitein and daidzein have an inhibitory effect on E2-realted endometrial carcinogenesis in mice, possibly by suppression of c-fos/jun, IL-1α and TNF-α.
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