کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5559632 | 1561688 | 2017 | 8 صفحه PDF | دانلود رایگان |
- TCEP induces senescence in the human L02 hepatocytes.
- TCEP-induced cellular senescence is regulated via activation of the p21Waf1/Cip1-Rb pathway.
- TCEP regulated expression of p21Waf1/Cip1 and Rb and lead to p53-independent senescence.
Tris (2-chloroethyl) phosphate (TCEP) has been widely used as a plasticizer and flame retardant. TCEP as a potential carcinogen is often detected in the occupational and nature environments. To investigate effects of TCEP on human hepatocytes, we assessed cell growth rate, cellular membrane integrity, senescence-associated β-galactosidase (SA-β-Gal) activity and analyzed expression of regulators involved in the p53-p21Waf1/Cip1-Rb pathway in TCEP-treated L02 cells. The results showed TCEP increased the percentage of SA-β-Gal positive cells, decreased IL-6 levels, down-regulated the regulators of p38MAPK-NF-κB pathways, but up-regulated the regulators of p21Waf1/Cip1-Rb pathway in L02 cells. Furthermore, we measured the SA-β-Gal activity and expression of regulators involved in the p53-p21Waf1/Cip1-Rb pathway in L02âp53 cells and p53-null Hep3B cells. Similar results were found in L02âp53 cells and Hep3B cells. The findings demonstrated that TCEP induced senescence-like growth arrest via the p21Waf1/Cip1-Rb pathway in a p53-independent manner, without activation of the IL-6/IL6R, p38MAPK-NF-κB pathways in hepatocytes.
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Journal: Environmental Toxicology and Pharmacology - Volume 56, December 2017, Pages 68-75