Cellular accumulation and lipid binding of perfluorinated alkylated substances (PFASs) – A comparison with lysosomotropic drugs. (1st February 2018)

• Record Type: Journal Article
• Authors: Sanchez Garcia, Diana; Sjödin, Marcus; Hellstrandh, Magnus; Norinder, Ulf; Nikiforova, Violetta; Lindberg, Johan; Wincent, Emma; Bergman, Åke; Cotgreave, Ian; Munic Kos, Vesna
• Is Part Of: Chemico-biological interactions. Volume 281(2018)
• Page Start: 1
• Page End: 10
• Publication Date: 2018-02-01
• Subjects: Bioaccumulation -- Perfluorinated compounds -- PFOS -- Cationic amphiphilic drugs -- Adipocytes -- Phospholipid binding; ACC compound's accumulation in cells -- ACE acetaminophen -- ACN acetonitrile -- AMIO amiodarone -- AMIT amitriptyline -- AZI azithromycin -- AZAG azithromycin-aglycon -- CAD cationic amphiphilic drug -- CHIIAM7.4 chromatographic index of immobilized artificial membrane at pH7.4 -- CHL chloroquine -- DMSO dimethylsulphoxide -- ERY erythromycin -- FBS fetal bovine serum -- FLU fluoxetine -- IAM immobilized artificial membrane -- IMI imipramine -- IND indomethacin -- LogD7.4 distribution coeficient of total charged and non-charged species of compound between octanol and water at pH7.4 -- LogP LogKOW -- distribution coeficient of non-charged species of compound between octanol and water NH4Ac -- ammonium acetate OFL -- ofloxacin PFASs -- perfluoroalkyl substances perfluorinated alkylated substances -- PFBS perfluorobutane sulfonic acid -- PFHxA perfluorohexanoic acid -- PFOA perfluorooctanoic acid -- PFOS perfluorooctane sulfonic acid -- POP persistent organic pollutant -- RET compound's retention in cells -- SD standard deviation -- TP total cellular proteins; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.12.021
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Many chemicals accumulate in organisms through a variety of different mechanisms. Cationic amphiphilic drugs (CADs) accumulate in lysosomes and bind to membranes causing phospholipidosis, whereas many lipophilic chemicals target adipose tissue. Perfluoroalkyl substances (PFASs) are widely used as surfactants, but many of them are highly bioaccumulating and persistent in the environment, making them notorious environmental toxicants. Understanding the mechanisms of their bioaccumulation is, therefore, important for their regulation and substitution with new, less harmful chemicals. We compared the highly bioaccumulative perfluorooctanesulfonic acid PFOS to its three less bioaccumulative alternatives perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA) and perfluorobutane sulfonic acid (PFBS), in their ability to accumulate and remain in lung epithelial cells (NCI-H292) and adipocytes (3T3-L1K) in vitro. As a reference point we tested a set of cationic amphiphilic drugs (CADs), known to highly accumulate in cells and strongly bind to phospholipids, together with their respective non-CAD controls. Finally, all compounds were examined for their ability to bind to neutral lipids and phospholipids in cell-free systems. Cellular accumulation and retention of the test compounds were highly correlated between the lung epithelial cells and adipocytes. Interestingly, although an anion itself, intensities of PFOS accumulation and retention in cells were comparable to those of CAD compounds, but PFOS failed to induce phospholipidosis or alter lysosomal volume. Compared to other lipophilicity measures, phospholipophilicity shows the highest correlation (Rˆ2 = 0.75) to cellular accumulation data in both cell types and best distinguishes between high and low accumulating compounds. This indicates that binding to phospholipids may be the most important component in driving high cellular accumulation in lung epithelial cells, as well as in adipocytes, and for both CADs and bioaccumulating PFASs. Obtained continuous PLS models based on compound's affinity for phospholipids and neutral lipids can be used as good prediction models of cellular accumulation and retention of PFASs and CADs. Highlights: PFOS accumulates in lung epithelial cells and adipocytes in amounts similar to CADs. Accumulation of CADs and PFASs highly correlates among lung cells and adipocytes. Binding to phospholipids is critical for PFAS and CAD accumulation in cells. PFAS accumulation in cells can be predicted from their phospholipo- and lipophilicity.