期刊
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
卷 30, 期 5, 页码 249-257出版社
WILEY-BLACKWELL
DOI: 10.1002/jbt.21786
关键词
Organophosphate Flame Retardants; Endocrine Disruptor; Androgen Receptor; Estrogen Receptor; Aryl Hydrocarbon Receptor; LNCaP
资金
- NSERC
- Chemical Management Plan of Environment Canada
- CIHR/Terry Fox Program Project
The effects of six organophosphate flame retardants (OPFRs) tris(2-butoxyethyl) phosphate, tris(2-chloroethyl) phosphate, tris(1-chloro-2-propyl) phosphate, tris(methylphenyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), and triethyl phosphate on the activities of androgen receptor (AR), estrogen receptor (ER), and aryl hydrocarbon receptor (AhR) were assessed in human prostate and endometrial cancer cells. OPFRs had no effect on ER or AhR target gene activation in ECC-1 cells. The effect of TDCIPP on mRNA and protein accumulation of AR target genes was examined further. AR-inducible gene and protein expression were significantly altered by TDCIPP exposure and repressed PSA levels in conditioned media of prostate cancer cells. We demonstrated that TDCIPP has no affinity for the AR ligand binding domain (AR-LBD) and exerts its antiandrogenic effects in a noncompetitive fashion. Thus, the clinical relevance of TDCIPP exposure on prostate cancer detection and progression to a therapeutically refractile state ought to be investigated further. (C) 2015 Wiley Periodicals, Inc.
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