Soybean isoflavone extract suppresses early but not later promotion of hepatocarcinogenesis by phenobarbital in female rat liver

Kwang Won Lee, H. J. Wang, P. A. Murphy, S. Hendrich

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31 Citations (Scopus)


The antioxidant and anticarcinogenic activities of soybean isoflavone extracts were investigated in female F344/N rats. Diethylnitrosamine (DEN, 15 mg/kg body wt) as a cancer initiator was injected intraperitoneally into 120 female F344/N rats at 10 days of age, and at weaning, phenobarbital (PB, 500 mg/kg diet) was fed to one-half of the rats. Soybean isoflavones were extracted in acetone-0.1 N HCl and analyzed by high-performance liquid chromatography, and two levels of soybean isoflavones (920 and 1,840 μmol/kg diet) were fed during PB treatment for 3 and 11 months. Control rats were fed diets without PB and with or without isoflavones. The effect of soybean isoflavone extract on hepatic glutathione peroxidase was measured, and development of γ-glutamyltransferase (GGT)-positive (GGT+) and placental glutathione transferase (PGST)-positive (PGST+) altered hepatic foci (AHF) was analyzed by computerized stereology. Soybean isoflavone extract providing 920 or 1,840 μmol/kg diet normalized total hepatic glutathione peroxidase activity, which was suppressed about 17% by PB (p < 0.05), and both doses of isoflavone extract suppressed PB promotion of hepatocarcinogenesis, decreasing the volume occupied by GGT+ and PGST+ AHF (p < 0.05) after three months. After 11 months of PB promotion, isoflavone extract at 920 μmol/kg diet decreased PGST+ AHF compared with the PB-fed group, but neither dose of isoflavone extract suppressed development of GGT+ AHF compared with the group fed PB alone. Furthermore the control group fed isoflavone extract at 1,840 μmol/kg diet showed greater development of GGT+ and PGST+ AHF than the group fed the basal diet alone. Therefore soybean isoflavones may be anticarcinogenic, but their margin of safety is relatively narrow, with a cancer-promoting dose of 1,840 μmol/kg in female F344/N rats initiated with DEN.

Original languageEnglish
Pages (from-to)267-278
Number of pages12
JournalNutrition and Cancer
Issue number3
Publication statusPublished - 1995 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)
  • Oncology

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