دورية أكاديمية
أعرض في EDS

Investigating the cytotoxicity of per- and polyfluoroalkyl substances in HepG2 cells: A structure-activity relationship approach.

التفاصيل البيبلوغرافية
العنوان: Investigating the cytotoxicity of per- and polyfluoroalkyl substances in HepG2 cells: A structure-activity relationship approach.
المؤلفون: Amstutz VH; Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, the Netherlands. Electronic address: v.amstutz@maastrichtuniversity.nl., Cengo A; Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, the Netherlands., Gehres F; Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, the Netherlands; Office for Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority (NVWA), 3540 AA Utrecht, the Netherlands., Sijm DTHM; Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, the Netherlands; Office for Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority (NVWA), 3540 AA Utrecht, the Netherlands., Vrolijk MF; Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, the Netherlands.
المصدر: Toxicology [Toxicology] 2022 Oct; Vol. 480, pp. 153312. Date of Electronic Publication: 2022 Sep 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Ireland NLM ID: 0361055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3185 (Electronic) Linking ISSN: 0300483X NLM ISO Abbreviation: Toxicology Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier
Original Publication: Amsterdam. Elsevier/North-Holland.
مواضيع طبية MeSH: Alkanesulfonic Acids* , Environmental Pollutants*/pharmacology , Fluorocarbons*/analysis , Fluorocarbons*/toxicity, Carbon ; Hep G2 Cells ; Humans ; Reactive Oxygen Species ; Structure-Activity Relationship
مستخلص: Per- and polyfluoroalkyl substances (PFAS) are a family of man-made chemicals with currently over 4'700 compounds identified. While toxicological data are available for some of the legacy PFAS, such as PFOA and PFOS, a knowledge gap remains concerning both emerging and legacy PFAS' toxicity due to the diversity of the PFAS. Therefore, a better understanding of the PFAS structure-activity relationship may prove helpful. The present study investigated a potential structure-activity relationship between PFAS and hepatotoxicity. As such, the effects of thirteen PFAS with varying carbon chain-length and functional head-groups (in a concentration range of 0-800 µM) on the cell viability of HepG2 cells and intracellular reactive oxygen species formation have been tested using the MTT and DCFH assay, respectively. The exposure times were either 3 or 24 h. In addition, intracellular PFAS levels were determined in HepG2 after 24 h exposure. The present study demonstrated that the cytotoxicity of PFAS is dependent on their chain-length as cell viability decreased with increasing chain-length at both exposure times. Calculated Relative Potency Factors (RPF), based on the TC 50 values, were used for a tentative ranking of PFAS regarding their hepatotoxicity: PFNA ˃ PFDA ˃ PFOS ≥ PFOA ˃ PFHxS ˃ PFBS ˃˃ PFHpA = PFHxA = PFBA = PFPrA = 6:2 FTOH = 4:2 = FTOH = 3:1 FTOH. Similar results were observed regarding intracellular reactive oxygen species generation at both exposure times, with a tentative ranking of: PFNA ˃ PFOS ˃ PFOA ≥ PFDA ˃ PFHxS ˃ PFBS ˃ PFBA ˃ PFHpA ≥ PFHxA ˃ PFPrA ˃ 6:2 FTOH = 4:2 FTOH = 3:1 FTOH. Moreover, a concentration-dependent reactive oxygen species generation has been observed for all PFSAs and PFCAs, but not for the FTOHs. In conclusion, the carbon chain-length and functional head-group of a PFAS determine their in vitro toxicity for the two toxicological endpoints assessed in the present study. Moreover, no effects were observed for the tested FTOHs. As such, the present study established a potential structure-activity relationship that opens the possibility of developing a predictive model to help with the risk assessment of PFAS in the future.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Cytotoxicity; Hepatotoxicity; In vitro; Oxidative stress; PFAS; Structure-activity
المشرفين على المادة: 0 (Alkanesulfonic Acids)
0 (Environmental Pollutants)
0 (Fluorocarbons)
0 (Reactive Oxygen Species)
7440-44-0 (Carbon)
تواريخ الأحداث: Date Created: 20220908 Date Completed: 20221011 Latest Revision: 20221102
رمز التحديث: 20240628
DOI: 10.1016/j.tox.2022.153312
PMID: 36075290
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-3185
DOI:10.1016/j.tox.2022.153312