Inhibition of dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis and induction of phase II enzymes by soy in female rats

Bioactive compounds in soy have been implicated for their role in the prevention of cancer, by acting as antioxidants or by inducing protective phase II enzymes, such as glutathione S-transferase (GST), UDP-glucuronosyltransferase (UDPGT), or quinone reductase (QR). To investigate potential mechanisms involved in the prevention of breast cancer, female Sprague-Dawley rats were fed purified AIN-93G with casein (control) or soy with 3 levels of isoflavonoids (0.03, 0.4, or 0.81 mg/g food; low, medium, and high iso, respectively). After 2 weeks, enzyme activity was determined from a subset of rats (n=6-7) from each diet group. Liver glutathione peroxidase (GSHPx) and glutathione reductase (GSHr); blood glutathione (GSH); kidney GST; and colon QR were all increased in rats consuming the high iso diet compared to control diet (p<0.05). Liver and blood GSH:GSSG (oxidized GSH) was lower in rats on the high iso diet compared to those on the low iso diet (p<0.05). Kidney QR and liver, kidney, small intestine, and colon UDPGT were increased in rats on the high iso diet compared to control and low iso diets (p<0.05). Another subset of rats (n=86) were fed diets for 2 weeks and intubated with DMBA or peanut oil and palpated weekly for tumors. At 100 days, plasma GST was increased in rats on the high iso diet compared to control diet in DMBA and control groups (p<0.05). Colon QR, GST, and UDPGT were increased in rats on the high iso diet compared to control and low iso diets (p<0.05). There was an inverse relationship between tumor number and increased isoflavone concentration (2.21, 1.36, 1.0, 0.67 tumors/ rat consuming control, low, medium, and high iso diets, respectively). In vivo antioxidant activity of soy is suggested by the increase of GSHPx, GSHr, GSH and decrease in GSSG. This data supports the mechanism of soy and soy isoflavones as phase II enzyme inducers and tumor inhibitors.