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

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 23; no. 3; pp. 383 - 390
• Main Authors: Murray, Tessa J., Maffini, Maricel V., Ucci, Angelo A., Sonnenschein, Carlos, Soto, Ana M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2007
• Subjects: Animals; Animals, Newborn; Benzhydryl Compounds; Bisphenol A; Carcinogenesis; Carcinoma in situ; 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 gland; 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; Rat; Rats; Rats, Wistar; Time Factors; Xenoestrogen; Bisphenol A; Mammary gland; Rat; Carcinoma in situ; Xenoestrogen; Carcinogenesis
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2006.10.002

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
μg 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-α 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.