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 replacement therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a]anthracene (DMBA)-induced mammary tumor development was investigated in wild-type (ER alpha WT) and estrogen receptor-alpha 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 subscapular implantation of medroxyprogesterone acetate. No tumors were observed in ER alpha KO mice. In ER alpha WT mice, dietary intake of genistein influenced tumor development, enhancing anaplasia of mammary cancer. Mice consuming genistein expressed malignant mammary adenocarcinoma, whereas benign adenomas 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 genistein 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 less 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 adverse effect on tumor development when high levels of genistein are consumed.
Day
J K
JK
Genetics Area Program, Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
Besch-Williford
C
C
McMann
T R
TR
Hufford
M G
MG
Lubahn
D B
DB
MacDonald
R S
RS
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000139:chemically induced*; D000818:Animals; D002364:Caseins / Q000008:administration & dosage; D004032:Diet; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010053:Ovary / Q000473:pathology; D011960:Receptors, Estrogen / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012878:Skin Neoplasms / Q000139:chemically induced; D014599:Uterus / Q000473:pathology; D015430:Weight Gain
D002364:Caseins; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I; D017258:Medroxyprogesterone Acetate; D019833:Genistein