Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons
| العنوان: | Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons |
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| المؤلفون: | R. Beaudoin, Alexandre R.R. Pery, Jean Pierre Cravedi, M. Audebert, Florence Anna Zeman |
| المساهمون: | ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut National de l'Environnement Industriel et des Risques (INERIS), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Audebert, Marc |
| المصدر: | Toxicology and Applied Pharmacology Toxicology and Applied Pharmacology, Elsevier, 2012, 260 (1), pp.58-64. ⟨10.1016/j.taap.2012.01.022⟩ Toxicology and Applied Pharmacology 1 (260), 58-64. (2012) |
| بيانات النشر: | HAL CCSD, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | GENOTOXICITY, Model parameters, 010501 environmental sciences, Toxicology, medicine.disease_cause, Polycyclic aromatic hydrocarbons Modelization Toxic Equivalent Factor Genotoxicity H2AX HepG2 LS-174T, EQUIVALENCY FACTORS TEFS, CANCER-RISK ASSESSMENT, IN-VIVO GENOTOXICITY, HUMAN CELL-LINES, DNA-DAMAGE, GAMMA-H2AX ASSAY, DOSE-RESPONSE, COAL-TAR, FLUORANTHENE, CARCINOGENICITY, 01 natural sciences, Histones, HEPG2, 03 medical and health sciences, TOXIC EQUIVALENT FACTOR, Cancer risk assessment, Cell Line, Tumor, POLYCYCLIC AROMATIC HYDROCARBONS, medicine, Humans, Potency, H2AX, Relative potency, 030304 developmental biology, 0105 earth and related environmental sciences, Pharmacology, 0303 health sciences, Dose-Response Relationship, Drug, Mutagenicity Tests, Chemistry, Low dose, Hep G2 Cells, Models, Theoretical, Human cell, Carcinogens, Environmental, 3. Good health, Environmental chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDE]Environmental Sciences, MODELIZATION, LS-174T, Genotoxicity |
| الوصف: | International audience; Polycyclic 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 (gammaH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0041-008X 1096-0333 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00a8af18010ee6c12feb2b524f405b20 https://hal-ineris.archives-ouvertes.fr/ineris-00963362 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....00a8af18010ee6c12feb2b524f405b20 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0041008X 10960333 |
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