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Genotoxic and enzymatic effects of fluoranthene in microsomes and freshly isolated hepatocytes from sole (Solea solea)

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Title: Genotoxic and enzymatic effects of fluoranthene in microsomes and freshly isolated hepatocytes from sole (Solea solea)
Authors: Wessel, N.1, Ménard, D.1, Pichavant-Rafini, K.2, Ollivier, H.2, Le Goff, J.3, Burgeot, T.1, Akcha, F.1 fakcha@ifremer.fr
Source: Aquatic Toxicology. Feb2012, Vol. 108, p33-41. 9p.
Subjects: Genetic toxicology, Fluoranthene, Microsomes, Liver cells, Aromatic compounds, Cytochromes, DNA adducts, Metabolites
Abstract: Abstract: The fluoranthene (Fluo) is one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in human food and in marine compartments. However, the existing data on its genotoxicity is poor and controversial. The aim of this study was to assess in vitro the potential genotoxicity of Fluo in sole and its possible effect on CYP450 modulation. Freshly isolated hepatocytes were exposed for 24h to a range of Fluo concentrations from 0.5 to 50μM in both culture flasks and microplate wells. The ethoxyresorufin-O-deethylase (EROD) activity was measured as an indicator of the activity of the cytochrome P450 1A1 (CYP1A1). The genotoxic effects were evaluated by measuring both DNA strand breaks and DNA adducts by the alkaline comet assay and the postlabeling technique respectively. Calf thymus DNA was also exposed to Fluo in the presence of sole liver microsomes in order to check for Fluo DNA adduct formation. In sole hepatocytes, Fluo was shown to induce a decrease in the EROD activity in a concentration-dependent manner. A significant genotoxic effect was observed in terms of DNA strand breakage from an exposure concentration of 5μM: despite a concentration-dependent effect was observed, it did not follow a linear dose-response. The response was similar whatever the way of exposure in flasks or in wells. One reproducible adduct was detected in the hepatocytes exposed to the highest concentrations of Fluo. The formation of Fluo adducts was confirmed by the detection of one reproducible adduct following in vitro exposure of calf thymus DNA to 100 and 200μM of Fluo in the presence of sole microsomes. These results demonstrate the potential of sole hepatocytes to metabolize Fluo in 24h into reactive species, able to induce genotoxicity by DNA strand breakage and DNA adduct formation. Moreover, a miniaturized cell exposure system was validated for further experiments using fewer amounts of hepatocytes and contaminants, and allowing exposure to PAH metabolites. [Copyright &y& Elsevier]
Copyright of Aquatic Toxicology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Genotoxic and enzymatic effects of fluoranthene in microsomes and freshly isolated hepatocytes from sole (Solea solea)
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  Data: <searchLink fieldCode="AR" term="%22Wessel%2C+N%2E%22">Wessel, N.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ménard%2C+D%2E%22">Ménard, D.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Pichavant-Rafini%2C+K%2E%22">Pichavant-Rafini, K.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Ollivier%2C+H%2E%22">Ollivier, H.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Le+Goff%2C+J%2E%22">Le Goff, J.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Burgeot%2C+T%2E%22">Burgeot, T.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Akcha%2C+F%2E%22">Akcha, F.</searchLink><relatesTo>1</relatesTo><i> fakcha@ifremer.fr</i>
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  Data: <searchLink fieldCode="JN" term="%22Aquatic+Toxicology%22">Aquatic Toxicology</searchLink>. Feb2012, Vol. 108, p33-41. 9p.
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  Data: <searchLink fieldCode="DE" term="%22Genetic+toxicology%22">Genetic toxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Fluoranthene%22">Fluoranthene</searchLink><br /><searchLink fieldCode="DE" term="%22Microsomes%22">Microsomes</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+cells%22">Liver cells</searchLink><br /><searchLink fieldCode="DE" term="%22Aromatic+compounds%22">Aromatic compounds</searchLink><br /><searchLink fieldCode="DE" term="%22Cytochromes%22">Cytochromes</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+adducts%22">DNA adducts</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolites%22">Metabolites</searchLink>
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  Label: Abstract
  Group: Ab
  Data: Abstract: The fluoranthene (Fluo) is one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in human food and in marine compartments. However, the existing data on its genotoxicity is poor and controversial. The aim of this study was to assess in vitro the potential genotoxicity of Fluo in sole and its possible effect on CYP450 modulation. Freshly isolated hepatocytes were exposed for 24h to a range of Fluo concentrations from 0.5 to 50μM in both culture flasks and microplate wells. The ethoxyresorufin-O-deethylase (EROD) activity was measured as an indicator of the activity of the cytochrome P450 1A1 (CYP1A1). The genotoxic effects were evaluated by measuring both DNA strand breaks and DNA adducts by the alkaline comet assay and the postlabeling technique respectively. Calf thymus DNA was also exposed to Fluo in the presence of sole liver microsomes in order to check for Fluo DNA adduct formation. In sole hepatocytes, Fluo was shown to induce a decrease in the EROD activity in a concentration-dependent manner. A significant genotoxic effect was observed in terms of DNA strand breakage from an exposure concentration of 5μM: despite a concentration-dependent effect was observed, it did not follow a linear dose-response. The response was similar whatever the way of exposure in flasks or in wells. One reproducible adduct was detected in the hepatocytes exposed to the highest concentrations of Fluo. The formation of Fluo adducts was confirmed by the detection of one reproducible adduct following in vitro exposure of calf thymus DNA to 100 and 200μM of Fluo in the presence of sole microsomes. These results demonstrate the potential of sole hepatocytes to metabolize Fluo in 24h into reactive species, able to induce genotoxicity by DNA strand breakage and DNA adduct formation. Moreover, a miniaturized cell exposure system was validated for further experiments using fewer amounts of hepatocytes and contaminants, and allowing exposure to PAH metabolites. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Aquatic Toxicology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.aquatox.2011.09.024
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 9
        StartPage: 33
    Subjects:
      – SubjectFull: Genetic toxicology
        Type: general
      – SubjectFull: Fluoranthene
        Type: general
      – SubjectFull: Microsomes
        Type: general
      – SubjectFull: Liver cells
        Type: general
      – SubjectFull: Aromatic compounds
        Type: general
      – SubjectFull: Cytochromes
        Type: general
      – SubjectFull: DNA adducts
        Type: general
      – SubjectFull: Metabolites
        Type: general
    Titles:
      – TitleFull: Genotoxic and enzymatic effects of fluoranthene in microsomes and freshly isolated hepatocytes from sole (Solea solea)
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            NameFull: Wessel, N.
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            NameFull: Ménard, D.
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            NameFull: Pichavant-Rafini, K.
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            NameFull: Le Goff, J.
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              M: 02
              Text: Feb2012
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              Y: 2012
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