Relative contribution of DNA strand breaks and DNA adducts to the genotoxicity of benzo[a]pyrene as a pure compound and in complex mixtures

Tarantini, Adeline; Maı̂tre, Anne; Lefebvre, Emmanuel; Marquès, Marie; Marie, Caroline; Ravanat, Jean‐Luc; Douki, Thierry

doi:10.1016/j.mrfmmm.2009.08.014

Cited by 93 publications

(51 citation statements)

References 49 publications

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“…Moreover, this assay was found to be more sensitive than the comet assay when we compare our results regarding PAHs genotoxicity with published data on the same cell line (Plazar et al, 2007;Winter et al, 2008;Tarantini et al, 2009). Concerning the comparison of the γ-H2AX assay with the micronucleus test, it is now well established that the micronucleus formation correlates well with H2AX phosphorylation (Medvedeva et al, 2007;Terradas et al, 2009;Yoshikawa et al, 2009).…”

Section: Genotoxicity Of Pahs In Human Cell Linessupporting

confidence: 58%

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons

Audebert

Zeman

Beaudoin

et al. 2012

Toxicology and Applied Pharmacology

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a b s t r a c t a r t i c l e i n f oPolycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (γH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24 h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose-response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment.

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Section: Genotoxicity Of Pahs In Human Cell Linessupporting

confidence: 58%

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons

Audebert

Zeman

Beaudoin

et al. 2012

Toxicology and Applied Pharmacology

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“…Despite their well documented toxic potential on humans and ecosystems (e.g. WHO, 2000;Billet et al, 2008;Andrysik et al, 2011;Tarantini et al, 2009;IARC, 2010), these compounds have been regulated only in few countries. In Europe, the Directive 2004/ 107/EC included the IARC class 1 human carcinogen benzo(a)pyrene (BaP) as indicator of particulate carcinogenic PAHs, by establishing an annual target value of 1 ng m À3 in PM 10 .…”

Section: Introductionmentioning

confidence: 99%

Seasonal trends and spatial variations of PM10-bounded polycyclic aromatic hydrocarbons in Veneto Region, Northeast Italy

Masiol

Formenton

Pasqualetto

et al. 2013

Atmospheric Environment

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“…Hepatotoxicity, nephrotoxicity, and hematologic alterations were among the major pathologies of BaP (Jung et al, 2010;Tarantini et al, 2009). Reproductive toxicity of the polyaromatic hydrocarbon has been investigated as well.…”

Section: Resultsmentioning

confidence: 99%

Antimutagenic Effects of Tannic Acid on Somatic and Germ Cells of Rats

Hassan¹,

El-Aziem²,

Barakat³

et al. 2011

Egyptian Journal of Genetics and Cytology

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Relative contribution of DNA strand breaks and DNA adducts to the genotoxicity of benzo[a]pyrene as a pure compound and in complex mixtures

Cited by 93 publications

References 49 publications

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons

Seasonal trends and spatial variations of PM10-bounded polycyclic aromatic hydrocarbons in Veneto Region, Northeast Italy

Antimutagenic Effects of Tannic Acid on Somatic and Germ Cells of Rats

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