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论文类型：期刊论文

发表时间：2011-06-01

发表刊物：TOXICOLOGICAL SCIENCES

收录刊物：Scopus、SCIE、PubMed

卷号：121

期号：2

页面范围：279-291

ISSN号：1096-6080

关键字：PFOS; BDE-47; developmental neurotoxicity; TR beta; BTEB; BDNF; GAP-43; NCAM1; thyroid hormone; TH-mediated transcription; combined toxicity

摘要：Perfluorooctane sulfonate (PFOS) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are two persistent environmental contaminants that are toxic to developing nervous systems, particularly via their disruption of thyroid hormone (TH) function. To investigate whether an interaction existed between PFOS and BDE-47 on TH-mediated pathways, adult female Wistar rats were exposed to 3.2 and 32 mg/kg of PFOS or BDE-47 in their diet and co-exposed to a combination of each chemical (3.2 mg/kg) from gestational day 1 to postnatal day (PND) 14. Serum and brain tissues from both male and female neonates were collected on PNDs 1, 7, and 14 to examine TH-regulated gene and protein expression. The results revealed that (1) a significant accumulation difference occurred between the two chemicals; (2) On a equimolar basis, BDE-47 and PFOS affected serum total triiodothyronine and total thyroxine differently in adults and offspring; (3) there were region-specific and exposure- and time-dependent alterations in TH concentrations and tested gene and protein expression levels; and (4) interaction for the combined chemicals was only observed for brain-derived neurotrophic factor (BDNF), which exhibited a synergistic effect on PND 1 in the cortex and an antagonistic effect on PND 14 in the hippocampus. Our results suggest a complex TH-mediated gene and protein response to BDE-47 and/or PFOS exposure that seems little related to TH homeostasis and that little combined interaction of co-exposures was observed except on BDNF. The underlying mechanisms remain uncertain but seem to involve more actions than just TH-regulated pathway.