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HERO ID
1249819
Reference Type
Journal Article
Title
Benzyl butyl phthalate induces necrosis by AhR mediation of CYP1B1 expression in human granulosa cells
Author(s)
Chen, HS; Chiang, PH; Wang, YC; Kao, MC; Shieh, TH; Tsai, CF; Tsai, EM
Year
2012
Is Peer Reviewed?
1
Journal
Reproductive Toxicology
ISSN:
0890-6238
EISSN:
1873-1708
Book Title
Reprod Toxicol.
Volume
33
Issue
1
Page Numbers
67-75
Language
English
PMID
22138065
DOI
10.1016/j.reprotox.2011.11.004
Web of Science Id
WOS:000300762700009
Abstract
We investigated the signaling pathway of the arylhydrocarbon receptor (AhR) on HO23 cells (immortalized human granulosa cells (hGC)) mediated by benzyl butyl-phthalate (BBP). BBP (1 μM) significantly increased the mRNA and protein levels of AhR, aryl hydrocarbon receptor nuclear translocator (ARNT) and cytochrome-P450 (CYP)1B1 in HO23 cells. Treatment with 3',4'-dimethoxyflavone (3',4'-DMF) or AhR siRNA significantly reduced AhR and CYP1B1, but CYP1A1 was not affected by 3',4'-DMF or AhR siRNA, suggesting that increases in CYP1A1 may not regulated by AhR. BBP induced the AhR fusion protein to localize and accumulate around the nucleus, and AhR heterodimerization with ARNT was observed in the nucleus by immunoprecipitation. Chromatin immunoprecipitation and reporter assays revealed the effect of BBP on CYP1B1, but not CYP1A1. Necrosis was significantly increased in HO23 cells after BBP treatment, and 3',4'-DMF, AhR siRNA or CYP1B1 siRNA knockdown blocked this phenomenon. These data suggest that BBP-induced HO23 cell necrosis is AhR and CYP1B1 dependent.
Keywords
Benzyl butyl phthalate; Human granulosa cell; Aryl hydrocarbon receptor; Cytochrome P450 1B1; Necrosis
Tags
IRIS
•
BBP (Butyl benzyl phthalate)
Literature Search
LitSearch Dec 2012
PubMed
WOS
Studies with Supporting Data
Mechanistic and genotoxicity studies
•
Phthalates – Targeted Search for Epidemiological Studies
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Pubmed
WOS
Toxnet
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Source – no date limit through June 2013 (Private)
Pubmed
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ToxNet
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