New in vitro biomarkers to detect toxicity in human placental cells: The example of benzo[A]pyrene

被引:15
作者
Wakx, Anais [1 ,2 ]
Regazzetti, Anne [1 ]
Dargere, Delphine [1 ]
Auzeil, Nicolas [1 ]
Gil, Sophie [2 ,3 ]
Evain-Brion, Daniele [2 ,3 ]
Laprevote, Olivier [1 ]
Rat, Patrice [1 ]
机构
[1] Univ Paris 05, Sorbonne Paris Cite, Fac Pharm, UMR 8638,CNRS,COMETE, 4 Ave Observ, F-75006 Paris, France
[2] Fdn PremUp, 4 Ave Observ, F-75014 Paris, France
[3] Univ Paris 05, Sorbonne Paris Cite, Fac Pharm, INSERM,U1139, 4 Ave Observ, F-75006 Paris, France
关键词
Benzo(a)pyrene; Placental cells; P2X7; receptor; In vitro; Toxicity; DNA damage; POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN CHORIONIC-GONADOTROPIN; DNA-DAMAGE; SER46; PHOSPHORYLATION; TROPHOBLAST INVASION; MEMBRANE-FLUIDITY; OXIDATIVE STRESS; RECEPTOR; EXPRESSION; APOPTOSIS;
D O I
10.1016/j.tiv.2015.11.022
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Our aim was to study the toxicity of benzo(a)pyrene (BaP), an environmental pollutant that can reach placenta, on two human placental models in order to propose biomarkers in risk assessment for pregnancy. Ex vivo human placental cells isolated from term placenta and JEG-3 cancer cell line were incubated with BaP at 0.1-10 mu M for 48 h or 72 h. BaP induced neither loss of cell viability nor apoptosis in ex vivo placental cells. To go further, we performed experiments on JEG-3 cell line that provides near-unlimited cells. The results we obtained in JEG-3 cells confirmed that BaP, in our experimental conditions, is neither necrotic nor apoptotic for placental cells. BaP toxicity on placental cells resulted in cell cycle arrest (G2/M phase) associated with inhibition of cell proliferation. Besides, we observed that BaP remodeled the protein content of membrane microdomains via increased expression of ZO-1, caveolin-1 and P2X7 cell degenerescence receptor. In conclusion, we identified nuclear and membrane potential biomarkers of risks for placenta and then pregnancy. These potential biomarkers detected on placental cell lines could represent useful tools for toxicological studies. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:76 / 85
页数:10
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