153 Mutagenesis, 2019, 34, 153–164 doi:10.1093/mutage/gez004 Original Manuscript Advance Access publication 10 March 2019 © The Author(s) 2019. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Original Manuscript The processes associated with lipid peroxidation in human embryonic lung fbroblasts, treated with polycyclic aromatic hydrocarbons and organic extract from particulate matter Pavel Rossner, Jr. 1, *, Helena Libalova 1 , Tereza Cervena 1,2 , Kristyna Vrbova 1 , Fatima Elzeinova 1 , Alena Milcova 1 , Andrea Rossnerova 1 , Zuzana Novakova 1 , Miroslav Ciganek 3 , Michaela Pokorna 1 , Antonin Ambroz 1 and Jan Topinka 1 1 Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 14220, Czech Republic, 2 Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic, 3 Department of Chemistry and Toxicology, Veterinary Research Institute, Brno 62100, Czech Republic *To whom correspondence should be addressed. Pavel Rossner, Jr., Department of Genetic Toxicology and Nanotoxicol- ogy, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, Prague 14220, Czech Republic. Tel: +420 241062596; Email: pavel.rossner@iem.cas.cz Received 10 December 2018; Revised 29 January 2019; Editorial decision 29 January 2019; Accepted 1 February 2019. Abstract Polycyclic aromatic hydrocarbons (PAHs) may cause lipid peroxidation via reactive oxygen species generation. 15-F 2t -isoprostane (IsoP), an oxidative stress marker, is formed from arachidonic acid (AA) by a free-radical induced oxidation. AA may also be converted to prostaglandins (PG) by prostaglandin-endoperoxide synthase (PTGS) induced by NF-κB. We treated human embryonic lung fbroblasts (HEL12469) with benzo[a]pyrene (B[a]P), 3-nitrobenzanthrone (3-NBA) and extractable organic matter (EOM) from ambient air particulate matter <2.5 µm for 4 and 24 h. B[a]P and 3-NBA induced expression of PAH metabolising, but not antioxidant enzymes. The concentrations of IsoP decreased, whereas the levels of AA tended to increase. Although the activity of NF-κB was not detected, the tested compounds affected the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). The levels of prostaglandin E 2 (PGE 2 ) decreased following exposure to B[a]P, whereas 3-NBA exposure tended to increase PGE 2 concentration. A distinct response was observed after EOM exposure: expression of PAH-metabolising enzymes was induced, IsoP levels increased after 24-h treatment but AA concentration was not affected. The activity of NF-κB increased after both exposure periods, and a signifcant induction of PTGS2 expression was found following 4-h treatment. Similarly to PAHs, the EOM exposure was associated with a decrease of PGE 2 levels. In summary, exposure to PAHs with low pro-oxidant potential results in a decrease of IsoP levels implying ‘antioxidant’ properties. For such compounds, IsoP may not be a suitable marker of lipid peroxidation. Downloaded from https://academic.oup.com/mutage/article-abstract/34/2/153/5372984 by AV CR Fyziologicky ustav SVI knihov user on 30 May 2019