Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/4936 |
Resumo: | Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effect of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr) and three halogenated derivatives of these compounds (1-ClPyr; 1-BrPyr and 7-ClBaA) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic MTT and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72h; except for multiple dose exposure to BaA and 7-ClBaA (1μM per day during 4 days) and single exposure to 10 μM BaA. Furthermore, selective mitochondrial and lysosomal toxicity was observed for Pyr and BaA series, respectively. In order to understand the underlying molecular mechanisms responsible for this effect ROS production, mitochondrial membrane depolarization, lysosomal pH, DNA fragmentation, early and late apoptosis mediators were evaluated after exposure to single doses of the compounds. All compounds were able to trigger oxidative stress after 24h as measured by catalase activity and a good correlation was found between mitochondrial membrane depolarization, lysosomal pH increase and MTT and neutral red assays, respectively. The evaluation of cell death mediators showed that caspase-3/7 but not annexin-V pathways were involved in toxicity triggered by the studied compounds. The integration of all results showed that 1-BrPyr and BaA have a higher toxicity potential. |
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Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell linePolycyclic Aromatic Hydrocarbons (PAHs)CytotoxicityBioaccumulationOrganic ContaminantsToxic EffectsWater DisinfectionProgrammed Cell DeathGenotoxicidade AmbientalPolycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effect of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr) and three halogenated derivatives of these compounds (1-ClPyr; 1-BrPyr and 7-ClBaA) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic MTT and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72h; except for multiple dose exposure to BaA and 7-ClBaA (1μM per day during 4 days) and single exposure to 10 μM BaA. Furthermore, selective mitochondrial and lysosomal toxicity was observed for Pyr and BaA series, respectively. In order to understand the underlying molecular mechanisms responsible for this effect ROS production, mitochondrial membrane depolarization, lysosomal pH, DNA fragmentation, early and late apoptosis mediators were evaluated after exposure to single doses of the compounds. All compounds were able to trigger oxidative stress after 24h as measured by catalase activity and a good correlation was found between mitochondrial membrane depolarization, lysosomal pH increase and MTT and neutral red assays, respectively. The evaluation of cell death mediators showed that caspase-3/7 but not annexin-V pathways were involved in toxicity triggered by the studied compounds. The integration of all results showed that 1-BrPyr and BaA have a higher toxicity potential.This work was supported by Fundação para a Ciência e a Tecnologia (FCT) [RECI/QEQ-MED/0330/2012] and Sílvia José work was supported by INSA [BRJ-DSA/2012].WileyRepositório Científico do Instituto Nacional de SaúdeMorgado, Patrícia I.Jose, SílviaWanke, RiccardoAntunes, Alexandra M.M.Sofia Cardoso, AnaJordao, Luisa2018-09-09T00:30:11Z2017-122017-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/4936engEnviron Toxicol Chem. 2017 Dec;36(12):3404-3414. doi: 10.1002/etc.3927. Epub 2017 Sep 8.730-726810.1002/etc.3927info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:40:31Zoai:repositorio.insa.pt:10400.18/4936Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:39:33.222819Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line |
title |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line |
spellingShingle |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line Morgado, Patrícia I. Polycyclic Aromatic Hydrocarbons (PAHs) Cytotoxicity Bioaccumulation Organic Contaminants Toxic Effects Water Disinfection Programmed Cell Death Genotoxicidade Ambiental |
title_short |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line |
title_full |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line |
title_fullStr |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line |
title_full_unstemmed |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line |
title_sort |
Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line |
author |
Morgado, Patrícia I. |
author_facet |
Morgado, Patrícia I. Jose, Sílvia Wanke, Riccardo Antunes, Alexandra M.M. Sofia Cardoso, Ana Jordao, Luisa |
author_role |
author |
author2 |
Jose, Sílvia Wanke, Riccardo Antunes, Alexandra M.M. Sofia Cardoso, Ana Jordao, Luisa |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Morgado, Patrícia I. Jose, Sílvia Wanke, Riccardo Antunes, Alexandra M.M. Sofia Cardoso, Ana Jordao, Luisa |
dc.subject.por.fl_str_mv |
Polycyclic Aromatic Hydrocarbons (PAHs) Cytotoxicity Bioaccumulation Organic Contaminants Toxic Effects Water Disinfection Programmed Cell Death Genotoxicidade Ambiental |
topic |
Polycyclic Aromatic Hydrocarbons (PAHs) Cytotoxicity Bioaccumulation Organic Contaminants Toxic Effects Water Disinfection Programmed Cell Death Genotoxicidade Ambiental |
description |
Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effect of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr) and three halogenated derivatives of these compounds (1-ClPyr; 1-BrPyr and 7-ClBaA) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic MTT and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72h; except for multiple dose exposure to BaA and 7-ClBaA (1μM per day during 4 days) and single exposure to 10 μM BaA. Furthermore, selective mitochondrial and lysosomal toxicity was observed for Pyr and BaA series, respectively. In order to understand the underlying molecular mechanisms responsible for this effect ROS production, mitochondrial membrane depolarization, lysosomal pH, DNA fragmentation, early and late apoptosis mediators were evaluated after exposure to single doses of the compounds. All compounds were able to trigger oxidative stress after 24h as measured by catalase activity and a good correlation was found between mitochondrial membrane depolarization, lysosomal pH increase and MTT and neutral red assays, respectively. The evaluation of cell death mediators showed that caspase-3/7 but not annexin-V pathways were involved in toxicity triggered by the studied compounds. The integration of all results showed that 1-BrPyr and BaA have a higher toxicity potential. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-12 2017-12-01T00:00:00Z 2018-09-09T00:30:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/4936 |
url |
http://hdl.handle.net/10400.18/4936 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Environ Toxicol Chem. 2017 Dec;36(12):3404-3414. doi: 10.1002/etc.3927. Epub 2017 Sep 8. 730-7268 10.1002/etc.3927 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132134477135872 |