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Cytotoxicity of hexahelicene and its effect on the aryl hydrocarbon receptor pathway.

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    0502150 - ÚCHP 2020 RIV GB eng J - Článek v odborném periodiku
    Vrba, J. - Roubalová, L. - Církva, Vladimír - Storch, Jan - Vacek, J.
    Cytotoxicity of hexahelicene and its effect on the aryl hydrocarbon receptor pathway.
    Toxicology in Vitro. Roč. 57, June 2019 (2019), s. 105-109. ISSN 0887-2333. E-ISSN 1879-3177
    Grant CEP: GA MPO FV10082
    Institucionální podpora: RVO:67985858
    Klíčová slova: PAH * helicene * biological activity
    Obor OECD: Biochemistry and molecular biology
    Impakt faktor: 2.959, rok: 2019
    Způsob publikování: Omezený přístup

    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.
    Trvalý link: http://hdl.handle.net/11104/0294118

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