Environmental six-ring polycyclic aromatic hydrocarbons are potent inducers of the AhR-dependent signaling in human cells

0537447 - BFÚ 2021 RIV GB eng J - Journal Article
Vondráček, Jan - Pěnčíková, K. - Ciganek, M. - Pivnička, Jakub - Karasová, Martina - Hýžďalová, Martina - Strapáčová, S. - Palková, L. - Neca, J. - Matthews, J. - Vojtíšek-Lom, M. - Topinka, Jan - Milcová, Alena - Machala, M.
Environmental six-ring polycyclic aromatic hydrocarbons are potent inducers of the AhR-dependent signaling in human cells.
Environmental Pollution. Roč. 266, č. 2020 (2020), č. článku 115125. ISSN 0269-7491. E-ISSN 1873-6424
R&D Projects: GA ČR(CZ) GA16-17085S; GA MŠMT(CZ) LO1508
Institutional support: RVO:68081707 ; RVO:68378041
Keywords : standard reference materials * molecular-weight 302 * particulate matter * estrogen-receptor * urban dust * metabolic-activation * differential action * equivalency factors * AhR
OECD category: Cell biology; Cell biology (UEM-P)
Impact factor: 8.071, year: 2020
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0269749120326178?via%3Dihub

The toxicities of many environmental polycyclic aromatic hydrocarbons (PAHs), in particular those of high-molecular-weight PAHs (with MW higher than 300), remain poorly characterized. The objective of this study was to evaluate the ability of selected environmentally relevant PAHs with MW 302 (MW302 PAHs) to activate the aryl hydrocarbon receptor (AhR), since this represents a major toxic mode of action of PAHs. A large number of the evaluated compounds exhibited strong AhR-mediated activities, in particular in human models. The studied MW302 PAHs also significantly contributed to the overall calculated AhR activities of complex environmental mixtures, including both defined standard reference materials and collected diesel exhaust particles. The high AhR-mediated activities of representative MW302 PAHs, e.g. naphtho[1,2-k]fluoranthene, corresponded with the modulation of expression of relevant AhR target genes in a human lung cell model, or with the AhR-dependent suppression of cell cycle progression/proliferation in estrogen-sensitive cells. This was in a marked contrast with the limited genotoxicity of the same compound(s). Given the substantial levels of the AhR-activating MW302 PAHs in combustion particles, it seems important to continue to investigate the toxic modes of action of this large group of PAHs associated with airborne particulate matter. (C) 2020 Elsevier Ltd. All rights reserved.
Permanent Link: http://hdl.handle.net/11104/0315184