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Article ; Online: Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen.

Martins, Carla / de Oliveira Galvão, Marcos Felipe / Costa, Pedro M / Dreij, Kristian

Environmental toxicology and pharmacology

2024 Volume 108, Page(s) 104453

Abstract: Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. ...

Abstract	Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC
Language	English
Publishing date	2024-04-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1318302-3
ISSN	1872-7077 ; 1382-6689
ISSN (online)	1872-7077
ISSN	1382-6689
DOI	10.1016/j.etap.2024.104453
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Zs.A 4490: Show issues

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Article ; Online: Determination of whole mixture-based potency factors for cancer risk assessment of complex environmental mixtures by in vitro testing of standard reference materials

de Oliveira Galvão, Marcos Felipe / Sadiktsis, Ioannis / Marques Pedro, Tiago / Dreij, Kristian

Environment International. 2022 Aug., v. 166 p.107345-

2022

Abstract: Whole mixture-based testing using in vitro new approach methodologies (NAMs) has been suggested to facilitate the hazard and risk assessment of complex environmental mixtures. Previous studies have shown that phosphorylation of DNA damage signaling ... ...

Abstract	Whole mixture-based testing using in vitro new approach methodologies (NAMs) has been suggested to facilitate the hazard and risk assessment of complex environmental mixtures. Previous studies have shown that phosphorylation of DNA damage signaling proteins checkpoint kinase 1 (pChk1) and histone 2AX (γH2AX) are sensitive markers that can be used for estimating carcinogenicity potencies in vitro. Here, and with the aim to better validate the applicability, in vitro-based Mixture Potency Factors (MPFs) of Standard Reference Materials (SRMs) from environmental polycyclic aromatic hydrocarbon (PAH)-containing mixtures were determined and compared to published mutagenicity and tumorigenicity data. Also, genotoxicity was assessed by a flow cytometry-based micronucleus (MN) assay which showed that only benzo[a]pyrene (B[a]P) and coal tar SRM (SRM1597a) caused dose-dependent increases of MN formation, while extracts of diesel particulate matter (SRM1650b), diesel particulate extract (SRM1975), and urban dust (SRM1649b) did not. However, a dose-dependent activation of DNA damage signaling was observed for all PAHs and SRMs. The results demonstrated that all SRMs were more potent than B[a]P, at B[a]P-equivalent concentrations, to induce pChk1 and γH2AX, and that western blot was more sensitive than the In-Cell Western assay in detecting their activation in response to these complex mixtures. Relative MPFs, based on dose–response modelling of pChk1 and γH2AX, ranged 113 – 5270 for the SRMs, indicating several orders of magnitude higher genotoxic potential than B[a]P. Moreover, these MPFs were in good agreement with potency values based on published data from Salmonella mutagenicity and in vivo carcinogenicity studies. In conclusion, these comparisons further validate the feasibility of applying in vitro NAMs, such as whole-mixture based MPFs, in cancer risk assessment of complex mixtures.
Keywords	DNA damage ; Salmonella ; Western blotting ; carcinogenicity ; coal tar ; dose response ; dust ; environment ; genotoxicity ; histones ; mutagenicity ; mutagens ; particulates ; phosphorylation ; polycyclic aromatic hydrocarbons ; risk assessment ; Standard reference material ; Mixture potency factors ; DNA damage signaling ; Cancer risk assessment
Language	English
Dates of publication	2022-08
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2022.107345
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Article ; Online: Determination of whole mixture-based potency factors for cancer risk assessment of complex environmental mixtures by in vitro testing of standard reference materials.

de Oliveira Galvão, Marcos Felipe / Sadiktsis, Ioannis / Marques Pedro, Tiago / Dreij, Kristian

Environment international

2022 Volume 166, Page(s) 107345

Abstract	Whole mixture-based testing using in vitro new approach methodologies (NAMs) has been suggested to facilitate the hazard and risk assessment of complex environmental mixtures. Previous studies have shown that phosphorylation of DNA damage signaling proteins checkpoint kinase 1 (pChk1) and histone 2AX (γH2AX) are sensitive markers that can be used for estimating carcinogenicity potencies in vitro. Here, and with the aim to better validate the applicability, in vitro-based Mixture Potency Factors (MPFs) of Standard Reference Materials (SRMs) from environmental polycyclic aromatic hydrocarbon (PAH)-containing mixtures were determined and compared to published mutagenicity and tumorigenicity data. Also, genotoxicity was assessed by a flow cytometry-based micronucleus (MN) assay which showed that only benzo[a]pyrene (B[a]P) and coal tar SRM (SRM1597a) caused dose-dependent increases of MN formation, while extracts of diesel particulate matter (SRM1650b), diesel particulate extract (SRM1975), and urban dust (SRM1649b) did not. However, a dose-dependent activation of DNA damage signaling was observed for all PAHs and SRMs. The results demonstrated that all SRMs were more potent than B[a]P, at B[a]P-equivalent concentrations, to induce pChk1 and γH2AX, and that western blot was more sensitive than the In-Cell Western assay in detecting their activation in response to these complex mixtures. Relative MPFs, based on dose-response modelling of pChk1 and γH2AX, ranged 113 - 5270 for the SRMs, indicating several orders of magnitude higher genotoxic potential than B[a]P. Moreover, these MPFs were in good agreement with potency values based on published data from Salmonella mutagenicity and in vivo carcinogenicity studies. In conclusion, these comparisons further validate the feasibility of applying in vitro NAMs, such as whole-mixture based MPFs, in cancer risk assessment of complex mixtures.
Language	English
Publishing date	2022-06-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2022.107345
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Article ; Online: A yearlong monitoring campaign of polycyclic aromatic compounds and other air pollutants at three sites in Sweden: Source identification, in vitro toxicity and human health risk assessment.

Sadiktsis, Ioannis / de Oliveira Galvão, Marcos Felipe / Mustafa, Musatak / Toublanc, Michaël / Ünlü Endirlik, Burcu / Silvergren, Sanna / Johansson, Christer / Dreij, Kristian

Chemosphere

2023 Volume 332, Page(s) 138862

Abstract: Air pollution is a complex mixture of gases and particulate matter (PM) with local and non-local emission sources, resulting in spatiotemporal variability in concentrations and composition, and thus associated health risks. To study this in the greater ... ...

Abstract	Air pollution is a complex mixture of gases and particulate matter (PM) with local and non-local emission sources, resulting in spatiotemporal variability in concentrations and composition, and thus associated health risks. To study this in the greater Stockholm area, a yearlong monitoring campaign with in situ measurements of PM
MeSH term(s)	Humans ; Air Pollutants/toxicity ; Air Pollutants/analysis ; Polycyclic Compounds/analysis ; Sweden ; Environmental Monitoring/methods ; Air Pollution/analysis ; Particulate Matter/toxicity ; Particulate Matter/analysis ; Vehicle Emissions/toxicity ; Vehicle Emissions/analysis ; Organic Chemicals/analysis ; Seasons ; Risk Assessment
Chemical Substances	Air Pollutants ; Polycyclic Compounds ; Particulate Matter ; Vehicle Emissions ; Organic Chemicals
Language	English
Publishing date	2023-05-05
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2023.138862
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Article ; Online: Reactive oxygen species-dependent transient induction of genotoxicity by retene in human liver HepG2 cells.

Scaramboni, Caroline / Arruda Moura Campos, Maria Lucia / Junqueira Dorta, Daniel / Palma de Oliveira, Danielle / Batistuzzo de Medeiros, Silvia Regina / de Oliveira Galvão, Marcos Felipe / Dreij, Kristian

Toxicology in vitro : an international journal published in association with BIBRA

2023 Volume 91, Page(s) 105628

Abstract: Retene is a polycyclic aromatic hydrocarbon (PAH) emitted mainly by biomass combustion, and despite its ubiquity in atmospheric particulate matter (PM), studies concerning its potential hazard to human health are still incipient. In this study, the ... ...

Abstract	Retene is a polycyclic aromatic hydrocarbon (PAH) emitted mainly by biomass combustion, and despite its ubiquity in atmospheric particulate matter (PM), studies concerning its potential hazard to human health are still incipient. In this study, the cytotoxicity and genotoxicity of retene were investigated in human HepG2 liver cells. Our data showed that retene had minimal effect on cell viability, but induced DNA strand breaks, micronuclei formation, and reactive oxygen species (ROS) formation in a dose- and time-dependent manner. Stronger effects were observed at earlier time points than at longer, indicating transient genotoxicity. Retene activated phosphorylation of Checkpoint kinase 1 (Chk1), an indicator of replication stress and chromosomal instability, which was in accordance with increased formation of micronuclei. A protective effect of the antioxidant N-acetylcysteine (NAC) towards ROS generation and DNA damage signaling was observed, suggesting oxidative stress as a key mechanism of the observed genotoxic effects of retene in HepG2 cells. Altogether our results suggest that retene may contribute to the harmful effects caused by biomass burning PM and represent a potential hazard to human health.
MeSH term(s)	Humans ; Reactive Oxygen Species ; Hep G2 Cells ; Particulate Matter ; DNA Damage ; Oxidative Stress ; Liver
Chemical Substances	retene (0W2D2E1P9Q) ; Reactive Oxygen Species ; Particulate Matter
Language	English
Publishing date	2023-06-09
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2023.105628
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Zs.A 2223: Show issues

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Article ; Online: Polycyclic aromatic compounds in particulate matter and indoor dust at preschools in Stockholm, Sweden: Occurrence, sources and genotoxic potential in vitro.

Lim, Hwanmi / Sadiktsis, Ioannis / de Oliveira Galvão, Marcos Felipe / Westerholm, Roger / Dreij, Kristian

The Science of the total environment

2020 Volume 755, Issue Pt 1, Page(s) 142709

Abstract: Children spend a significant amount of their day in preschool; thus, environmental quality at preschools may have an impact on children's health. In the present study, we analyzed polycyclic aromatic compounds (PACs), including PAHs, alkylated PAHs and ... ...

Abstract	Children spend a significant amount of their day in preschool; thus, environmental quality at preschools may have an impact on children's health. In the present study, we analyzed polycyclic aromatic compounds (PACs), including PAHs, alkylated PAHs and oxygenated PAHs (OPAHs), in indoor and outdoor air particulate matter (PM
MeSH term(s)	Air Pollutants/analysis ; Air Pollutants/toxicity ; Air Pollution, Indoor/analysis ; Child ; Child, Preschool ; DNA Damage ; Dust/analysis ; Environmental Monitoring ; Humans ; Particulate Matter/analysis ; Particulate Matter/toxicity ; Polycyclic Aromatic Hydrocarbons/analysis ; Polycyclic Aromatic Hydrocarbons/toxicity ; Polycyclic Compounds ; Sweden
Chemical Substances	Air Pollutants ; Dust ; Particulate Matter ; Polycyclic Aromatic Hydrocarbons ; Polycyclic Compounds
Language	English
Publishing date	2020-10-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2020.142709
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Article: Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting

de Oliveira Galvão, Marcos Felipe / Sadiktsis, Ioannis / Batistuzzo de Medeiros, Silvia Regina / Dreij, Kristian

Environmental pollution. 2020 Jan., v. 256

2020

Abstract: Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) ...

Abstract	Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs; ii) intracellular levels of reactive oxygen species (ROS); iii) genotoxic effects and time- and dose-dependent activation of DNA damage signaling, and iv) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair, using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8–10 ng/m3), while benzanthrone and 9,10-anthraquinone were the most abundant oxy-PAHs. Testing of PM extracts was based on B[a]P equivalent doses (B[a]Peq). IC50 values for viability were 5.7 and 3.0 nM B[a]Peq at 24 h and 48 h, respectively. At these low doses, we observed a time- and dose-dependent increase in intracellular levels of ROS, genotoxicity (DNA strand breaks) and DNA damage signaling (phosphorylation of the protein checkpoint kinase 1 – Chk1). In comparison, effects of B[a]P alone was observed at micromolar range. To our knowledge, no previous study has demonstrated an activation of pChk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro, in lung cells exposed to cashew nut roasting extracts. Sustained induction of expression of several important stress response mediators of xenobiotic metabolism (CYP1A1, CYP1B1), ROS and pro-inflammatory response (IL-8, TNF-α, IL-2, COX2), and DNA damage response (CDKN1A and DDB2) was also identified. In conclusion, our data show high potency of cashew nut roasting PM to induce cellular stress including genotoxicity, and more potently when compared to B[a]P alone. Our study provides new data that will help elucidate the toxic effects of low-levels of PAH mixtures from air PM generated by cashew nut roasting.
Keywords	DNA damage ; DNA repair ; air pollution ; anthracenes ; benzo(a)pyrene ; biomarkers ; carcinogenicity ; cashew nuts ; cell cycle checkpoints ; dose response ; gene expression ; gene expression regulation ; genotoxicity ; inflammation ; inhibitory concentration 50 ; interleukin-2 ; interleukin-8 ; lungs ; metabolism ; particulates ; phosphorylation ; protein kinases ; quinones ; reactive oxygen species ; roasting ; stress response ; traditional technology ; tumor necrosis factor-alpha ; viability ; xenobiotics
Language	English
Dates of publication	2020-01
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	280652-6
ISSN	1873-6424 ; 0013-9327 ; 0269-7491
ISSN (online)	1873-6424
ISSN	0013-9327 ; 0269-7491
DOI	10.1016/j.envpol.2019.113381
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Article ; Online: In vitro cytotoxicity and genotoxicity of single and combined pesticides used by Bolivian farmers.

Barrón Cuenca, Jessika / de Oliveira Galvão, Marcos Felipe / Ünlü Endirlik, Burcu / Tirado, Noemi / Dreij, Kristian

Environmental and molecular mutagenesis

2021 Volume 63, Issue 1, Page(s) 4–17

Abstract: We previously showed that farmers in Bolivia are exposed to many pesticides, some at elevated levels, and that this was associated with increased risk of genetic damage. To improve the understanding of possible mixture effects, the cytotoxicity and ... ...

Abstract	We previously showed that farmers in Bolivia are exposed to many pesticides, some at elevated levels, and that this was associated with increased risk of genetic damage. To improve the understanding of possible mixture effects, the cytotoxicity and genotoxicity of pesticides were studied in vitro using human liver HepG2 cells. The studied pesticides were 2,4-D, chlorpyrifos, cypermethrin, glyphosate, methamidophos, paraquat, profenofos, and tebuconazole. Three mixtures (U1, U2, and U3) were based on profiles of urinary pesticide metabolites and one mixture on the most frequently used pesticides (S1). The results showed that paraquat and methamidophos were the most cytotoxic pesticides (EC
MeSH term(s)	Bolivia ; Chlorpyrifos/toxicity ; DNA Damage ; Farmers ; Humans ; Paraquat/toxicity ; Pesticides/toxicity
Chemical Substances	Pesticides ; Chlorpyrifos (JCS58I644W) ; Paraquat (PLG39H7695)
Language	English
Publishing date	2021-12-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639145-x
ISSN	1098-2280 ; 0893-6692
ISSN (online)	1098-2280
ISSN	0893-6692
DOI	10.1002/em.22468
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Article ; Online: Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting.

de Oliveira Galvão, Marcos Felipe / Sadiktsis, Ioannis / Batistuzzo de Medeiros, Silvia Regina / Dreij, Kristian

Environmental pollution (Barking, Essex : 1987)

2019 Volume 256, Page(s) 113381

Abstract	Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs; ii) intracellular levels of reactive oxygen species (ROS); iii) genotoxic effects and time- and dose-dependent activation of DNA damage signaling, and iv) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair, using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8-10 ng/m
MeSH term(s)	A549 Cells ; Air Pollutants/analysis ; Air Pollutants/toxicity ; Anacardium/chemistry ; Biomass ; Checkpoint Kinase 1/genetics ; DNA Damage ; Dose-Response Relationship, Drug ; Humans ; Nuts/chemistry ; Particulate Matter/analysis ; Particulate Matter/toxicity ; Polycyclic Aromatic Hydrocarbons/analysis ; Polycyclic Aromatic Hydrocarbons/toxicity ; Signal Transduction ; Time Factors
Chemical Substances	Air Pollutants ; Particulate Matter ; Polycyclic Aromatic Hydrocarbons ; CHEK1 protein, human (EC 2.7.11.1) ; Checkpoint Kinase 1 (EC 2.7.11.1)
Language	English
Publishing date	2019-10-15
Publishing country	England
Document type	Journal Article
ZDB-ID	280652-6
ISSN	1873-6424 ; 0013-9327 ; 0269-7491
ISSN (online)	1873-6424
ISSN	0013-9327 ; 0269-7491
DOI	10.1016/j.envpol.2019.113381
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Article ; Online: Erratum to "Cell death pathways of particulate matter toxicity" Chemosphere 188C (2017) 32-48.

Peixoto, Milena Simões / de Oliveira Galvão, Marcos Felipe / Batistuzzo de Medeiros, Silvia Regina

Chemosphere

2018 Volume 193, Page(s) 1243

Language	English
Publishing date	2018
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2017.11.071
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