TY - JOUR
T1 - Comparisons of brain, uterus, and liver mRNA expression for cytochrome P450s, DNA methyltransferase-1, and catechol-o-methyltransferase; in prepubertal female sprague-dawley rats exposed to a mixture of aryl hydrocarbon receptor agonists
AU - Desaulniers, Daniel
AU - Xiao, G. H.
AU - Leingartner, K.
AU - Chu, I.
AU - Musicki, B.
AU - Tsang, B. K.
N1 - Funding Information:
The authors are grateful to L. Casavant, Dr. M. Charbonneau, J. Cole, Dr. G. Douglas, A. Lee, Y. Li, T. Odorozzi, K. Pazterko, L. Shao, Dr. K. Soumano, Dr. R. Vincent, and G. Zu for their technical advice and assistance, and to Drs. Guillaume Pelletier and Raymond Poon for suggested improvements to the manuscript. This study was funded by Health Canada, Toxic Substances Research Initiative (TSRI) grant no. 045 and Northern Contaminants Program (NCP) grant no. H16-2004.
PY - 2005/7
Y1 - 2005/7
N2 - Non-ortho polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) are ubiquitous environmental contaminants that exert their toxicity mostly through activation of the aryl-hydrocarbon receptor (AhR), and are referred to as AhR agonists. The objective was to study, by real time reverse-transcriptase-polymerase chain reaction (RT-PCR), the effects of postnatal exposure to a reconstituted mixture of AhR agonists present in breast milk (3 non-ortho PCBs, 6 PCDDs, and 7 PCDFs, referred to hereinafter as AhRM) on mRNA expression of estrogen receptor (ERα), enzymes involved with the metabolism of estrogens [catechol-o-methyltransferase (Comt), cytochrome P450 (Cyp)1A1, 1B1 and 2B1], and DNA methyltransferase-1 (Dnmt1), in brain areas, liver and uterus of immature female rats. Neonates were exposed by gavage during postnatal day (PND) 1-20 with dosages equivalent to 1, 10, 100, and 1000 times the estimated average human exposure level, and were sacrificed at PND 21. None of the end points were affected in uterine cross-sections, or in samples of uterine tissue layers collected by laser capture microdissection. At 1000 times, the AhRM reduced Dnmt1 mRNA abundance to 28% and 32% of control in the liver and hypothalamus, respectively. In the brain, Cyp1A1 was increased (409%) but ERα was reduced (66%). Similarly, mRNA abundance for Comt isoforms was reduced in the liver (45%) and brain areas (55-70%). AhRM at 100×, the lowest effective dose, exerted a 220% increase in brain cortex Comt [membrane bound (Mb)], a 219% increase in hepatic Cyp1B1, and a 63% decrease in hepatic Comt (soluble (S)+Mb). These results support the possibility that early exposure to environmental contaminants could lead to effects mediated by changes in DNA methylation and/or estrogen metabolism and signaling.
AB - Non-ortho polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) are ubiquitous environmental contaminants that exert their toxicity mostly through activation of the aryl-hydrocarbon receptor (AhR), and are referred to as AhR agonists. The objective was to study, by real time reverse-transcriptase-polymerase chain reaction (RT-PCR), the effects of postnatal exposure to a reconstituted mixture of AhR agonists present in breast milk (3 non-ortho PCBs, 6 PCDDs, and 7 PCDFs, referred to hereinafter as AhRM) on mRNA expression of estrogen receptor (ERα), enzymes involved with the metabolism of estrogens [catechol-o-methyltransferase (Comt), cytochrome P450 (Cyp)1A1, 1B1 and 2B1], and DNA methyltransferase-1 (Dnmt1), in brain areas, liver and uterus of immature female rats. Neonates were exposed by gavage during postnatal day (PND) 1-20 with dosages equivalent to 1, 10, 100, and 1000 times the estimated average human exposure level, and were sacrificed at PND 21. None of the end points were affected in uterine cross-sections, or in samples of uterine tissue layers collected by laser capture microdissection. At 1000 times, the AhRM reduced Dnmt1 mRNA abundance to 28% and 32% of control in the liver and hypothalamus, respectively. In the brain, Cyp1A1 was increased (409%) but ERα was reduced (66%). Similarly, mRNA abundance for Comt isoforms was reduced in the liver (45%) and brain areas (55-70%). AhRM at 100×, the lowest effective dose, exerted a 220% increase in brain cortex Comt [membrane bound (Mb)], a 219% increase in hepatic Cyp1B1, and a 63% decrease in hepatic Comt (soluble (S)+Mb). These results support the possibility that early exposure to environmental contaminants could lead to effects mediated by changes in DNA methylation and/or estrogen metabolism and signaling.
KW - Catechol-o-methyltransferase
KW - DNA methyltransferase
KW - Polychlorinated dibenzodioxins
KW - Polychlorinated dibenzofurans
KW - Rat
KW - Uterus
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UR - http://www.scopus.com/inward/citedby.url?scp=26944468327&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfi178
DO - 10.1093/toxsci/kfi178
M3 - Article
C2 - 15858227
AN - SCOPUS:26944468327
SN - 1096-6080
VL - 86
SP - 175
EP - 184
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -