Effect of dietary soy isoflavone aglycones on the urinary 16alpha-to-2-hydroxyestrone ratio in C3H/HeJ mice.
Estradiol is metabolized through two mutually exclusive pathways. 2-Hydroxyestrone (2-OHE,) is antiestrogenic, while 16alpha-hydroxyestrone (16alpha-OHE1) is a potent estrogen. It is suggested that a high urinary 16alpha-OHE1-to-2-OHE1 rato is a biomarker of increased mammary tumor risk. Mice were fed one of the test diets for 21 days. Indole-3-carbinol (2,500 mg/kg diet) increased the cytochrome P-450 content of hepatic microsomes and liver weight and reduced the urinary 16alpha-OHE1-to-2-OHE1 ratio in comparison with the respective value in the control mice. Fermented soy extract (100, 200, or 400 mg isoflavonoid/kg diet), genistein (200 mg/kg diet), and daidzein (200 mg/kg diet) each reduced the urinary 16alpha-OHE1-to-2-OHE1 ratio without increasing the cytochrome P-450 content of hepatic microsomes or liver weight. The combination of genistein and daidzein (100 mg and 100 mg/kg diet) did not have a synergistic effect on the reduction in urinary 16alpha-OHE1-to-2-OHE1 ratio. These data suggest that the soy isoflavonoid aglycones genistein and daidzein and indole-3-carbinol each exert a cancer-preventive effect by shifting metabolism away from the production of genotoxic metabolites toward the production of inactive metabolites.
Kishida
T
T
Department of Biological Resources, Faculty of Agriculture, Ehime University, Matsuyama, Japan.
Beppu
M
M
Nashiki
K
K
Izumi
T
T
Ebihara
K
K
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000652:urine; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006894:Hydroxyestrones / Q000652:urine*; D007211:Indoles / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size; D010936:Plant Extracts / Q000494:pharmacology; D013025:Glycine max
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D006894:Hydroxyestrones; D007211:Indoles; D007529:Isoflavones; D010936:Plant Extracts; C026702:16-hydroxyestrone; C004742:daidzein; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol; D019833:Genistein; C024980:2-hydroxyestrone