title: Effects of oral exposure to bisphenol A on gene expression and global genomic DNA methylation in the prostate, female mammary gland, and uterus of NCTR Sprague-Dawley rats.
abstract: Bisphenol A (BPA), an industrial chemical used in the manufacture of polycarbonate and epoxy resins, binds to the nuclear estrogen receptor with an affinity 4-5 orders of magnitude lower than that of estradiol. We reported previously that "high BPA" [100,000 and 300,000 µg/kg body weight (bw)/day], but not "low BPA" (2.5-2700 µg/kg bw/day), induced clear adverse effects in NCTR Sprague-Dawley rats gavaged daily from gestation day 6 through postnatal day (PND) 90. The "high BPA" effects partially overlapped those of ethinyl estradiol (EE2, 0.5 and 5.0 µg/kg bw/day). To evaluate further the potential of "low BPA" to induce biological effects, here we assessed the global genomic DNA methylation and gene expression in the prostate and female mammary glands, tissues identified previously as potential targets of BPA, and uterus, a sensitive estrogen-responsive tissue. Both doses of EE2 modulated gene expression, including of known estrogen-responsive genes, and PND 4 global gene expression data showed a partial overlap of the "high BPA" effects with those of EE2. The "low BPA" doses modulated the expression of several genes; however, the absence of a dose response reduces the likelihood that these changes were causally linked to the treatment. These results are consistent with the toxicity outcomes.
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Electronic address: luisa.camacho@fda.hhs.gov.
authors: Luísa
authors: L
authors: Camacho
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Mallikarjuna S
authors: MS
authors: Basavarajappa
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Ching-Wei
authors: CW
authors: Chang
authors: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Tao
authors: T
authors: Han
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Tetyana
authors: T
authors: Kobets
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Igor
authors: I
authors: Koturbash
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Gordon
authors: G
authors: Surratt
authors: Office of Scientific Coordination, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Sherry M
authors: SM
authors: Lewis
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Michelle M
authors: MM
authors: Vanlandingham
authors: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: James C
authors: JC
authors: Fuscoe
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Gonçalo
authors: G
authors: Gamboa da Costa
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: Igor P
authors: IP
authors: Pogribny
authors: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors: K Barry
authors: KB
authors: Delclos
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000633:toxicity*; D002853:Chromatography, Liquid; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D015870:Gene Expression; D023281:Genomics / Q000379:methods; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage* / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003176:Complement C3; D004997:Ethinyl Estradiol; D008780:Methyltransferases; D010636:Phenols; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D064030:S100 Calcium Binding Protein G; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Ethinyl estradiol; Global genomic DNA methylation; Mammary gland; Microarray; Prostate