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