title: Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis.
abstract: Prepubertal exposure to a pharmacological dose (500 mg kg(-1)) of the phyto-oestrogen genistein can reduce the incidence and multiplicity of carcinogen-induced mammary tumours in rats. However, such an exposure also disrupts the function of the hypothalamic-pituitary-gonadal axis, making it unsuitable for breast cancer prevention. We studied whether prepubertal exposure to genistein at a total body dose broadly comparable to the level typical of Oriental countries, approximately 1 mg kg(-1) body weight, affects mammary tumorigenesis. We also studied whether prepubertal exposure to zearalenone, a major source for phyto-oestrogens in the USA, influences breast cancer risk. Prepubertal rats were treated between postnatal days 7 and 20, with 20 microg (approximately 1 mg kg(-1) body weight) of either genistein or zearalenone. Zearalenone exposure significantly reduced both the incidence and multiplicity of mammary tumours induced by 7,12-dimethylbenz(a)anthracene (DMBA). Genistein exposure significantly reduced tumour multiplicity, but not tumour incidence, when compared with vehicle-treated animals. Furthermore, 60% of the tumours in the genistein group were not malignant, while all the tumours analysed for histopathology in the vehicle and zearalenone groups were adenocarcinomas. A higher number of differentiated alveolar buds, and lower number of terminal ducts, were present in the DMBA-treated mammary glands of the phyto-oestrogen exposed rats. The concentration of oestrogen receptor (ER) binding sites after the DMBA treatment was low in the mammary glands of all groups but a significantly higher proportion of the glands in the zearalenone exposed rats were ER-positive (i.e. ER levels > or = 5 fmol mg(-1) protein) than the glands of the vehicle controls. Our data suggest that a prepubertal exposure to a low dose of either zearalenone or genistein may protect the mammary gland from carcinogen-induced malignant transformation, possibly by increasing differentiation of the mammary epithelial tree.
authors.affiliation: Lombardi Cancer Center, Department of Psychiatry, Georgetown University, Washington, DC 20007, USA.
authors.forename: L
authors.initials: L
authors.lastname: Hilakivi-Clarke
authors.forename: I
authors.initials: I
authors.lastname: Onojafe
authors.forename: M
authors.initials: M
authors.lastname: Raygada
authors.forename: E
authors.initials: E
authors.lastname: Cho
authors.forename: T
authors.initials: T
authors.lastname: Skaar
authors.forename: I
authors.initials: I
authors.lastname: Russo
authors.forename: R
authors.initials: R
authors.lastname: Clarke
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D012741:Sexual Maturation; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects; D015025:Zearalenone / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D011960:Receptors, Estrogen; D015127:9,10-Dimethyl-1,2-benzanthracene; D015025:Zearalenone; D019833:Genistein