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Effects of Defined Mixtures of Persistent Organic Pollutants (POPs) on Pre-lethal Cytotoxicity in the Human A-498 Kidney Cell Line In Vitro
Exposure and Health ( IF 4.5 ) Pub Date : 2021-05-10 , DOI: 10.1007/s12403-021-00396-7
Mazia Amber , Yuling Xie , Hanne Friis Berntsen , Karin Elizabeth Zimmer , Erik Ropstad , Steven Verhaegen , Lisa Connolly

A total mixture of 29 persistent organic pollutants (POPs) modelled from Scandinavian blood concentrations was used to expose human A-498 kidney cells for 24 h over a concentration range spanning below to above blood level (1/10x, 1x, 50x, 100x, 500x). Its constituent submixtures (PFAA, Br, Cl) and co-mixtures (PFAA + Br, PFAA + Cl, Br + Cl) were also tested. Valinomycin (12 µM) was used as a cytotoxic comparative compound. Cell number (CN), nuclear area (NA), nuclear intensity (NI), mitochondrial membrane potential (MMP), and mitochondrial mass (MM) were assessed using high content analysis (HCA). Only the co-mixtures (PFAA + Cl, PFAA + Br) at 50x and 50x, 500x decreased CN, respectively. NI was increased by the total mixture at 500x and Cl mixture at all concentrations tested. MMP was increased by the total mixture at 100x and 500x, PFAA at 1x, Br + Cl and PFAA + Cl at 100x and 500x, respectively. MM was decreased by the total mixture at 500x. In contrast, valinomycin decreased CN and surviving cells showed a decrease in MMP and an increase in MM. In conclusion, POP exposure altered mitochondrial metabolism and induced cell death via an alternative mechanism to valinomycin. Only specific combinations of individual chemical classes, but not the total mixture, affected cell number.



中文翻译:

持久性有机污染物(POPs)的特定混合物对人A-498肾脏细胞系体外致死前细胞毒性的影响

根据斯堪的纳维亚血药浓度建模的29种持久性有机污染物(POPs)的总混合物用于在范围低于或高于血药浓度(1 / 10x,1x,50x,100x, 500倍)。还测试了其组成子混合物(PFAA,Br,Cl)和共混合物(PFAA + Br,PFAA + Cl,Br + Cl)。Valinomycin(12 µM)被用作细胞毒性的比较化合物。使用高含量分析(HCA)评估细胞数(CN),核面积(NA),核强度(NI),线粒体膜电位(MMP)和线粒体质量(MM)。分别只有50x和50x,500x的共混物(PFAA + Cl,PFAA + Br)降低了CN。在所有测试浓度下,总混合物500倍的NI和Cl混合物的NI均增加。混合物的MMP值分别为100x和500x,PFAA为1x,Br + Cl和PFAA + Cl分别为100x和500x。MM在500x时降低了总混合物的量。相反,缬氨霉素降低了CN,存活细胞的MMP降低了,MM升高了。总之,POP暴露通过缬氨霉素的另一种机制改变了线粒体的代谢并诱导了细胞死亡。仅单个化学类别的特定组合,而不是总混合物,影响细胞数。

更新日期:2021-05-11
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