Dietary genistein increased DMBA-induced mammary adenocarcinoma in wild-type, but not ER alpha KO, mice

Dietary supplements containing concentrates of plant-derived estrogens are being increasingly used by consumers as alternatives for hormone replacemen t therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a] anthracene (DMBA)-induc ed mammary tumor development was investigated in wild-type (ER alpha WT) an d estrogen receptor-a knockout (ER alpha KO) mice. ER alpha WT and ER alpha KO mice were fed a casein-based diet containing 0 or 1 g genistein/kg diet from weaning. Tumors were induced by oral administration of DMBA and subsc apular implantation of medroxyprogesterone acetate. No tumors were observed in ER alpha KO mice. In ER alpha WT mice, dietary intake of genistein infl uenced tumor development, enhancing anaplasia of mammary cancer. Mice consu ming genistein expressed malignant mammary adenocarcinoma, whereas benign a denomas were observed in mice fed the control diet. Dietary intake was also influenced by genistein, with ER alpha WT and ER alpha KO mice fed geniste in consuming less food (p<0.0001) and subsequently weighing less than mice fed the control diet (p<0.0001). Significant differences in food intake by genotype were also observed (p=0.0017), with ER alpha KO mice consuming les s than ER alpha WT mice. Overall, this study found no protective effect of genistein on DMBA-induced mammary tumors in mice and suggests a potential a dverse effect on tumor development when high levels of genistein are consum ed.