2019
McCarrick, Sarah; Cunha, Virginia; Zapletal, Ondřej; Vondráček, Jan; Dreij, Kristian
In vitro and in vivo genotoxicity of oxygenated polycyclic aromatic hydrocarbons. Journal Article
In: Environmental pollution (Barking, Essex : 1987), vol. 246, pp. 678–687, 2019, ISSN: 1873-6424 0269-7491, (Place: England).
Abstract | Links | BibTeX | Tags: *DNA Damage, Animals, Cell Culture Techniques, Cell Survival/drug effects/genetics, Comet assay, Embryonic Development/drug effects/genetics, Environmental Monitoring/*methods, Epithelial Cells/drug effects/pathology, Genotoxicity, Hep G2 Cells, Humans, Micronucleus assay, Mutagens/analysis/*toxicity, Oxygen/chemistry, Oxygenated PAH, Polycyclic Aromatic Hydrocarbons/analysis/*toxicity, Zebrafish, Zebrafish/embryology
@article{mccarrick_vitro_2019,
title = {In vitro and in vivo genotoxicity of oxygenated polycyclic aromatic hydrocarbons.},
author = {Sarah McCarrick and Virginia Cunha and Ondřej Zapletal and Jan Vondráček and Kristian Dreij},
doi = {10.1016/j.envpol.2018.12.092},
issn = {1873-6424 0269-7491},
year = {2019},
date = {2019-03-01},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {246},
pages = {678–687},
abstract = {Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a group of environmental pollutants found in complex mixtures together with PAHs. In contrast to the extensively studied PAHs, which have been established to have mutagenic and carcinogenic properties, much less is known about the effects of oxy-PAHs. The present work aimed to investigate the genotoxic potency of a set of environmentally relevant oxy-PAHs along with environmental soil samples in human bronchial epithelial cells (HBEC). We found that all oxy-PAHs tested induced DNA strand breaks in a dose-dependent manner and some of the oxy-PAHs further induced micronuclei formation. Our results showed weak effects in response to the oxy-PAH containing subfraction of the soil sample. The genotoxic potency was confirmed in both HBEC and HepG2 cells following exposure to oxy-PAHs by an increased level of phospho-Chk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro. We further exposed zebrafish embryos to single oxy-PAHs or a binary mixture with PAH benzo[a]pyrene (B[a]P) and found the mixture to induce comparable or greater effects on the induction of DNA strand breaks compared to the sum of that induced by B[a]P and oxy-PAHs alone. In conclusion, oxy-PAHs were found to elicit genotoxic effects at similar or higher levels to that of B[a]P which indicates that oxy-PAHs may contribute significantly to the total carcinogenic potency of environmental PAH mixtures. This emphasizes further investigations of these compounds as well as the need to include oxy-PAHs in environmental monitoring programs in order to improve health risk assessment.},
note = {Place: England},
keywords = {*DNA Damage, Animals, Cell Culture Techniques, Cell Survival/drug effects/genetics, Comet assay, Embryonic Development/drug effects/genetics, Environmental Monitoring/*methods, Epithelial Cells/drug effects/pathology, Genotoxicity, Hep G2 Cells, Humans, Micronucleus assay, Mutagens/analysis/*toxicity, Oxygen/chemistry, Oxygenated PAH, Polycyclic Aromatic Hydrocarbons/analysis/*toxicity, Zebrafish, Zebrafish/embryology},
pubstate = {published},
tppubtype = {article}
}
Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a group of environmental pollutants found in complex mixtures together with PAHs. In contrast to the extensively studied PAHs, which have been established to have mutagenic and carcinogenic properties, much less is known about the effects of oxy-PAHs. The present work aimed to investigate the genotoxic potency of a set of environmentally relevant oxy-PAHs along with environmental soil samples in human bronchial epithelial cells (HBEC). We found that all oxy-PAHs tested induced DNA strand breaks in a dose-dependent manner and some of the oxy-PAHs further induced micronuclei formation. Our results showed weak effects in response to the oxy-PAH containing subfraction of the soil sample. The genotoxic potency was confirmed in both HBEC and HepG2 cells following exposure to oxy-PAHs by an increased level of phospho-Chk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro. We further exposed zebrafish embryos to single oxy-PAHs or a binary mixture with PAH benzo[a]pyrene (B[a]P) and found the mixture to induce comparable or greater effects on the induction of DNA strand breaks compared to the sum of that induced by B[a]P and oxy-PAHs alone. In conclusion, oxy-PAHs were found to elicit genotoxic effects at similar or higher levels to that of B[a]P which indicates that oxy-PAHs may contribute significantly to the total carcinogenic potency of environmental PAH mixtures. This emphasizes further investigations of these compounds as well as the need to include oxy-PAHs in environmental monitoring programs in order to improve health risk assessment.
2011
Gábelová, Alena; Valovičová, Zuzana; Mesárošová, Monika; Trilecová, Lenka; Hrubá, Eva; Marvanová, Soňa; Krčmár, Pavel; Milcová, Alena; Schmuczerová, Jana; Vondráček, Jan; Machala, Miroslav; Topinka, Jan
Genotoxicity of 7H-dibenzo[c,g]carbazole and its tissue-specific derivatives in human hepatoma HepG2 cells is related to CYP1A1/1A2 expression. Journal Article
In: Environmental and molecular mutagenesis, vol. 52, no. 8, pp. 636–645, 2011, ISSN: 1098-2280 0893-6692, (Place: United States).
Abstract | Links | BibTeX | Tags: Base Sequence, Blotting, Carbazoles/*toxicity, Cell Survival/drug effects, Chromosome-Defective/chemically induced/statistics & numerical data, Comet assay, Cytochrome P-450 CYP1A1/*genetics, Cytochrome P-450 CYP1A2/*genetics, DNA adducts, DNA Breaks, Dose-Response Relationship, Drug, Hep G2 Cells, Histones/metabolism, Humans, Micronuclei, Micronucleus Tests, Mitotic Index, Molecular Sequence Data, Mutagens/*toxicity, Phosphorylation, Real-Time Polymerase Chain Reaction, Tumor Suppressor Protein p53/metabolism, Western
@article{gabelova_genotoxicity_2011,
title = {Genotoxicity of 7H-dibenzo[c,g]carbazole and its tissue-specific derivatives in human hepatoma HepG2 cells is related to CYP1A1/1A2 expression.},
author = {Alena Gábelová and Zuzana Valovičová and Monika Mesárošová and Lenka Trilecová and Eva Hrubá and Soňa Marvanová and Pavel Krčmár and Alena Milcová and Jana Schmuczerová and Jan Vondráček and Miroslav Machala and Jan Topinka},
doi = {10.1002/em.20664},
issn = {1098-2280 0893-6692},
year = {2011},
date = {2011-10-01},
journal = {Environmental and molecular mutagenesis},
volume = {52},
number = {8},
pages = {636–645},
abstract = {The goal of this study was to investigate the genotoxicity of 7H-dibenzo[c,g]carbazole (DBC), a ubiquitous environmental pollutant, and its methyl derivatives, 5,9-dimethylDBC (DiMeDBC), a strict hepatocarcinogen, and N-methylDBC (N-MeDBC), a specific sarcomagen in human hepatoma HepG2 cells, and to infer potential mechanisms underlying the biological activity of particular carcinogen. All dibenzocarbazoles, regardless the tissue specificity, induced significant DNA strand break levels and micronuclei in HepG2 cells; though a mitotic spindle dysfunction rather than a chromosome breakage was implicated in N-MeDBC-mediated micronucleus formation. While DBC and N-MeDBC produced stable DNA adducts followed with p53 protein phosphorylation at Ser-15, DiMeDBC failed. A significant increase in DNA strand breaks following incubation of exposed cells with a repair-specific endonuclease (Fpg protein) suggested that either oxidative DNA damage or unstable DNA-adducts might underlie DiMeDBC genotoxicity in human hepatoma cells. DiMeDBC and N-MeDBC increased substantially also the amount of CYP1A1/2 expression in HepG2 cells. Pretreatment of cells with substances affecting AhR-mediated CYP1A family of enzymes expression; however, diminished DiMeDBC and N-MeDBC genotoxicity. Our data clearly demonstrated differences in the mechanisms involved in the biological activity of DiMeDBC and N-MeDBC in human hepatoma cells; the genotoxicity of these DBC derivatives is closely related to CYP1A1/2 expression.},
note = {Place: United States},
keywords = {Base Sequence, Blotting, Carbazoles/*toxicity, Cell Survival/drug effects, Chromosome-Defective/chemically induced/statistics & numerical data, Comet assay, Cytochrome P-450 CYP1A1/*genetics, Cytochrome P-450 CYP1A2/*genetics, DNA adducts, DNA Breaks, Dose-Response Relationship, Drug, Hep G2 Cells, Histones/metabolism, Humans, Micronuclei, Micronucleus Tests, Mitotic Index, Molecular Sequence Data, Mutagens/*toxicity, Phosphorylation, Real-Time Polymerase Chain Reaction, Tumor Suppressor Protein p53/metabolism, Western},
pubstate = {published},
tppubtype = {article}
}
The goal of this study was to investigate the genotoxicity of 7H-dibenzo[c,g]carbazole (DBC), a ubiquitous environmental pollutant, and its methyl derivatives, 5,9-dimethylDBC (DiMeDBC), a strict hepatocarcinogen, and N-methylDBC (N-MeDBC), a specific sarcomagen in human hepatoma HepG2 cells, and to infer potential mechanisms underlying the biological activity of particular carcinogen. All dibenzocarbazoles, regardless the tissue specificity, induced significant DNA strand break levels and micronuclei in HepG2 cells; though a mitotic spindle dysfunction rather than a chromosome breakage was implicated in N-MeDBC-mediated micronucleus formation. While DBC and N-MeDBC produced stable DNA adducts followed with p53 protein phosphorylation at Ser-15, DiMeDBC failed. A significant increase in DNA strand breaks following incubation of exposed cells with a repair-specific endonuclease (Fpg protein) suggested that either oxidative DNA damage or unstable DNA-adducts might underlie DiMeDBC genotoxicity in human hepatoma cells. DiMeDBC and N-MeDBC increased substantially also the amount of CYP1A1/2 expression in HepG2 cells. Pretreatment of cells with substances affecting AhR-mediated CYP1A family of enzymes expression; however, diminished DiMeDBC and N-MeDBC genotoxicity. Our data clearly demonstrated differences in the mechanisms involved in the biological activity of DiMeDBC and N-MeDBC in human hepatoma cells; the genotoxicity of these DBC derivatives is closely related to CYP1A1/2 expression.