Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure

Reprod Toxicol. Apr-May 2007;23(3):383-90. doi: 10.1016/j.reprotox.2006.10.002. Epub 2006 Oct 24.

Abstract

Exposure of the fetus to excess estrogen is believed to increase the risk of developing breast cancer during adult life. Fetal exposure to low doses of the xenoestrogen bisphenol A resulted in long-lasting effects in the mouse mammary gland that were manifested during adult life. It enhanced sensitivity to estradiol, decreased apoptosis, increased the number of progesterone receptor-positive epithelial cells at puberty and increased lateral branching at 4 months of age. We now report that fetal exposure to 2.5, 25, 250 and 1000 microg bisphenol A/kg body weight/day induces the development of ductal hyperplasias and carcinoma in situ at postnatal day 50 and 95 in rats. These highly proliferative lesions have an increased number of estrogen receptor-alpha positive cells. Thus, fetal bisphenol A exposure is sufficient to induce the development of preneoplastic and neoplastic lesions in the mammary gland in the absence of any additional treatment aimed at increasing tumor development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Benzhydryl Compounds
  • Carcinoma in Situ / chemically induced*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Dose-Response Relationship, Drug
  • Estrogen Receptor alpha / metabolism
  • Estrogens, Non-Steroidal / administration & dosage
  • Estrogens, Non-Steroidal / toxicity
  • Female
  • Fetal Development / drug effects
  • Hyperplasia
  • Immunochemistry
  • Male
  • Mammary Glands, Animal / chemistry
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / pathology
  • Mammary Neoplasms, Animal / chemically induced*
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology
  • Phenols / administration & dosage
  • Phenols / toxicity*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Benzhydryl Compounds
  • Estrogen Receptor alpha
  • Estrogens, Non-Steroidal
  • Phenols
  • bisphenol A