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Food Chem Toxicol. 2015 Jul;81:92-103. doi: 10.1016/j.fct.2015.04.009. Epub 2015 Apr 8.

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.

Author information

1
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.
2
Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
3
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
4
Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
5
Office of Scientific Coordination, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.

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.

KEYWORDS:

Bisphenol A; Ethinyl estradiol; Global genomic DNA methylation; Mammary gland; Microarray; Prostate

PMID:
25862956
PMCID:
PMC4487663
DOI:
10.1016/j.fct.2015.04.009
[Indexed for MEDLINE]
Free PMC Article

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