Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis

Br J Cancer. 1999 Aug;80(11):1682-8. doi: 10.1038/sj.bjc.6690584.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Cell Division / drug effects
  • Female
  • Genistein / pharmacology*
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / physiology
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estrogen / metabolism
  • Sexual Maturation*
  • Time Factors
  • Weight Gain / drug effects
  • Zearalenone / pharmacology*

Substances

  • Anticarcinogenic Agents
  • Receptors, Estrogen
  • 9,10-Dimethyl-1,2-benzanthracene
  • Zearalenone
  • Genistein