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Cytotoxicity of hexahelicene and its effect on the aryl hydrocarbon receptor pathway.
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SYSNO ASEP 0502150 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cytotoxicity of hexahelicene and its effect on the aryl hydrocarbon receptor pathway. Author(s) Vrba, J. (CZ)
Roubalová, L. (CZ)
Církva, Vladimír (UCHP-M) RID, ORCID, SAI
Storch, Jan (UCHP-M) RID, ORCID, SAI
Vacek, J. (CZ)Source Title Toxicology in Vitro. - : Elsevier - ISSN 0887-2333
Roč. 57, June 2019 (2019), s. 105-109Number of pages 5 s. Language eng - English Country GB - United Kingdom Keywords PAH ; helicene ; biological activity Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects FV10082 GA MPO - Ministry of Industry and Trade (MPO) Method of publishing Limited access Institutional support UCHP-M - RVO:67985858 UT WOS 000465050300013 EID SCOPUS 85062149211 DOI https://doi.org/10.1016/j.tiv.2019.02.020 Annotation Carbohelicenes are a group of helical-shaped polycyclic aromatic hydrocarbons. This study examined the effect of hexahelicene (or [6]helicene) and of its imidazolium derivative, 1-butyl-3-(2-methyl[6]helicenyl)-imidazolium bromide (I[6]H), on the activity of the aryl hydrocarbon receptor (AhR) and expression of cytochrome P450 1A1 (CYP1A1) in human hepatoma HepG2 cells. An MTT viability assay showed that both [6]helicene and I[6]H were cytotoxic to HepG2 cells after 24 h of exposure, with IC50 values of 0.9 and 8.4 μM, respectively. Using a gene reporter assay performed in transiently transfected HepG2 cells, we found that 1 μM [6]helicene, unlike I [6]H, significantly increased the activity of AhR to 2.1-fold compared to the control after 24 h of exposure. Moreover, [6]helicene induced a small but significant increase in the level of CYP1A1 mRNA. On the other hand, neither the protein level nor activity of CYP1A1 were affected by [6]helicene in HepG2 cells. The effect of [6] helicene on the AhR pathway was thus much lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent AhR activator. We conclude that [6]helicene is a poor activator of the AhR pathway in HepG2 cells, and that the possible activation of the AhR pathway in vivo remains to be investigated. Workplace Institute of Chemical Process Fundamentals Contact Eva Jirsová, jirsova@icpf.cas.cz, Tel.: 220 390 227 Year of Publishing 2020 Electronic address http://hdl.handle.net/11104/0294118
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