INHIBITION OF N-METHYL-N-NITROSOUREA-INDUCED MAMMARY-TUMORS IN RATS BY THE SOYBEAN ISOFLAVONES

Soy-based diets, rich in the isoflavones genistein and daidzein, are t hought to protect against breast and prostate cancer. We used the N-me thyl-N-nitrosourea (MNU)-induced mammary carcinogenesis animal model t o test the effectiveness of these two isoflavones as chemopreventive a gents. Each isoflavone was injected daily into 35-day-old rats for six months while we monitored the animals' body weight and mammary tumor appearance. Genistein was effective in reducing tumor multiplicity, bu t it reduced tumor incidence only marginally. Daidzein was less effect ive in reducing both tumor incidence and multiplicity. To investigate genistein's mechanism of action, we determined the topoisomerase II (t opo II) activity and detected the phosphotyrosine-containing peptides int eh extracts of mammary tissues isolated from control and isoflavon e-treated animals. Mammary tumors contained over 60-fold higher topo I I enzymatic activity than the mammary glands. Similarly, more tyrosine phosphopeptides were detectable in mammary tumors than in mammary gla nds. Tissue samples from genistein treated animals contained similar t opo II and protein tyrosine kinase (PTK) activities as the control gro up. These data suggest that mammary tumorigenesis is accompanied by an extensive increase in topo II and PTK activities. The mechanism of ch emoprevention by genistein, however, is independent of topo II or PTK inhibition.