Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats

Environmental exposure to bisphenol A (BPA) affects mammary gland development in rodents and primates. Prenatal exposure to environmentally relevant doses of BPA increased the number of intraductal hyperplasias and ductal carcinomas in situ by 50 days of age in Wistar-Furth rats. We aimed to determi...

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Published in:Environmental health perspectives 2013-09, Vol.121 (9), p.1040-1046
Main Authors: Acevedo, Nicole, Davis, Barbara, Schaeberle, Cheryl M, Sonnenschein, Carlos, Soto, Ana M
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adults
Animals
Benzhydryl Compounds - administration & dosage
Benzhydryl Compounds - blood
Benzhydryl Compounds - toxicity
Bisphenol A
Breast cancer
Carcinogens
Carcinogens, Environmental - administration & dosage
Carcinogens, Environmental - toxicity
Carcinoma, Ductal - chemically induced
Cocarcinogens
Dams
Drug dosages
Environmental aspects
Environmental Exposure - adverse effects
Estrogens
Exposure
Female
Females
Fetuses
Gestation
Hyperplasia
Hyperplasia - chemically induced
Identification and classification
Laboratory animals
Lesions
Mammary glands
Mammary Neoplasms, Animal - chemically induced
Offspring
Phenols - administration & dosage
Phenols - blood
Phenols - toxicity
Physiological aspects
Pregnancy
Production capacity
Rats
Rats, Inbred WF
Rats, Sprague-Dawley
Rodents
Studies
Toxicology
Vagina
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cited_by cdi_FETCH-LOGICAL-c811t-ec28b2015397083656dcbe7e3bf61f96e7f151f885319473f53ca62a8e5b2e283
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container_end_page 1046
container_issue 9
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container_title Environmental health perspectives
container_volume 121
creator Acevedo, Nicole
Davis, Barbara
Schaeberle, Cheryl M
Sonnenschein, Carlos
Soto, Ana M
description Environmental exposure to bisphenol A (BPA) affects mammary gland development in rodents and primates. Prenatal exposure to environmentally relevant doses of BPA increased the number of intraductal hyperplasias and ductal carcinomas in situ by 50 days of age in Wistar-Furth rats. We aimed to determine whether BPA exposure of dams during gestation only or throughout lactation affects the incidence of mammary gland neoplasia in female offspring. We treated pregnant Sprague-Dawley rats with BPA at 0, 0.25, 2.5, 25, or 250 μg BPA/kg BW/day from gestational day (GD) 9 to birth and from GD9 to postnatal day (PND) 21. Mammary glands from BPA-exposed offspring were examined at four time points for preneoplastic and neoplastic lesions. To assess circulating BPA levels, we exposed pregnant rats to vehicle or 250 μg BPA/kg BW/day during gestation only or during gestation/lactation and analyzed sera from dams, fetuses, and nursing pups for total and unconjugated BPA. Total and unconjugated BPA were detected in sera from 100% of dams and fetuses and 33% of pups exposed to 250 μg BPA/kg BW/day. Unconjugated BPA levels in exposed dams and fetuses (gestational) and in exposed dams and pups (gestational/lactational) were within levels found in humans. Preneoplastic lesions developed in BPA-exposed female offspring across all doses as early as PND50. Unexpectedly, mammary gland adenocarcinomas developed in BPA-exposed offspring by PND90. Our findings suggest that developmental exposure to environmentally relevant levels of BPA during gestation and lactation induces mammary gland neoplasms in the absence of any additional carcinogenic treatment. Thus, BPA may act as a complete mammary gland carcinogen.
doi_str_mv 10.1289/ehp.1306734
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Prenatal exposure to environmentally relevant doses of BPA increased the number of intraductal hyperplasias and ductal carcinomas in situ by 50 days of age in Wistar-Furth rats. We aimed to determine whether BPA exposure of dams during gestation only or throughout lactation affects the incidence of mammary gland neoplasia in female offspring. We treated pregnant Sprague-Dawley rats with BPA at 0, 0.25, 2.5, 25, or 250 μg BPA/kg BW/day from gestational day (GD) 9 to birth and from GD9 to postnatal day (PND) 21. Mammary glands from BPA-exposed offspring were examined at four time points for preneoplastic and neoplastic lesions. To assess circulating BPA levels, we exposed pregnant rats to vehicle or 250 μg BPA/kg BW/day during gestation only or during gestation/lactation and analyzed sera from dams, fetuses, and nursing pups for total and unconjugated BPA. Total and unconjugated BPA were detected in sera from 100% of dams and fetuses and 33% of pups exposed to 250 μg BPA/kg BW/day. 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Unconjugated BPA levels in exposed dams and fetuses (gestational) and in exposed dams and pups (gestational/lactational) were within levels found in humans. Preneoplastic lesions developed in BPA-exposed female offspring across all doses as early as PND50. Unexpectedly, mammary gland adenocarcinomas developed in BPA-exposed offspring by PND90. Our findings suggest that developmental exposure to environmentally relevant levels of BPA during gestation and lactation induces mammary gland neoplasms in the absence of any additional carcinogenic treatment. Thus, BPA may act as a complete mammary gland carcinogen.</abstract><cop>United States</cop><pub>National Institute of Environmental Health Sciences</pub><pmid>23876597</pmid><doi>10.1289/ehp.1306734</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0091-6765
ispartof Environmental health perspectives, 2013-09, Vol.121 (9), p.1040-1046
issn 0091-6765
1552-9924
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3764091
source GreenFILE; ABI/INFORM Global; ProQuest - Publicly Available Content Database; PubMed Central
subjects Adenocarcinoma
Adults
Animals
Benzhydryl Compounds - administration & dosage
Benzhydryl Compounds - blood
Benzhydryl Compounds - toxicity
Bisphenol A
Breast cancer
Carcinogens
Carcinogens, Environmental - administration & dosage
Carcinogens, Environmental - toxicity
Carcinoma, Ductal - chemically induced
Cocarcinogens
Dams
Drug dosages
Environmental aspects
Environmental Exposure - adverse effects
Estrogens
Exposure
Female
Females
Fetuses
Gestation
Hyperplasia
Hyperplasia - chemically induced
Identification and classification
Laboratory animals
Lesions
Mammary glands
Mammary Neoplasms, Animal - chemically induced
Offspring
Phenols - administration & dosage
Phenols - blood
Phenols - toxicity
Physiological aspects
Pregnancy
Production capacity
Rats
Rats, Inbred WF
Rats, Sprague-Dawley
Rodents
Studies
Toxicology
Vagina
title Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats
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