Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure.
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.
Murray
Tessa J
TJ
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, United States.
Maffini
Maricel V
MV
Ucci
Angelo A
AA
Sonnenschein
Carlos
C
Soto
Ana M
AM
D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D002278:Carcinoma in Situ / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006965:Hyperplasia; D007120:Immunochemistry; D008297:Male; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds