| 1. |
- Jatkowska, Natalia, et al.
(författare)
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Identification of synergistic and antagonistic actions of environmental pollutants : Bisphenols A, S and F in the presence of DEP, DBP, BADGE and BADGE center dot 2HCl in three component mixtures
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 767
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Tidskriftsartikel (refereegranskat)abstract
- Ecosystems are facing increased pressure due to the emission of many classes of emerging contaminants. However, very little is known about the interactions of these pollutants, such as bisphenols (BPs), plasticizers or pharmaceuticals. By employing bioluminescent bacteria (Microtox assay), we were able to define interactions between selected emerging pollutants (namely BPA, BPS, BPF, BADGE, BADGE center dot 2HCl, DEP, DBP) in ternary mixtures, at environmentally relevant concentration levels (down to as low as 1.89, 1.42. 3.08, and 0.3261AM for, respectively, BPA BPF, BPS and BADGE- 2HCl). We provide the first systematic analysis of bisphenols and phthalates in three component mixtures. Using this system, we performed toxicity modelling with concentration addition (CA) and independent action (IA) approaches, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. Interestingly, we mathematically and experimentally confirmed a novel synergy between BPA, BADGE and BADGE center dot 2HCl. The synergy of BPA, BADGE and BADGE center dot 2HCl is distinct, with both models suggesting these a nalytes have a similar mode of action (MOA). Moreover, we unexpectedly found a strong antagonistic impact with DEP, in mixtures containing BPA and BADGE analogues, which is confirmed with both mathematical models. Our study also shows that the impact of BPS and BPF in many mixtures is highly concentration dependent, justifying the necessity to perform mixture studies using wide concentration ranges. Overall, this study demonstrates that bioluminescent bacteria are a relevant model for detecting the synergistic and antagonist actions of environmental pollutants in mixtures, and highlights the importance of analyzing combinations of pollutants in higher order mixtures.
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| 2. |
- Kudlak, Blazej, et al.
(författare)
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Enhanced Toxicity of Bisphenols Together with UV Filters in Water : Identification of Synergy and Antagonism in Three-Component Mixtures
- 2022
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 27:10
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Tidskriftsartikel (refereegranskat)abstract
- Contaminants of emerging concern (CEC) localize in the biome in variable combinations of complex mixtures that are often environmentally persistent, bioaccumulate and biomagnify, prompting a need for extensive monitoring. Many cosmetics include UV filters that are listed as CECs, such as benzophenone derivatives (oxybenzone, OXYB), cinnamates (2-ethylhexyl 4-methoxycinnamate, EMC) and camphor derivatives (4-methylbenzylidene-camphor, 4MBC). Furthermore, in numerous water sources, these UV filters have been detected together with Bisphenols (BPs), which are commonly used in plastics and can be physiologically detrimental. We utilized bioluminescent bacteria (Microtox assay) to monitor these CEC mixtures at environmentally relevant doses, and performed the first systematic study involving three sunscreen components (OXYB, 4MBC and EMC) and three BPs (BPA, BPS or BPF). Moreover, a breast cell line and cell viability assay were employed to determine the possible effect of these mixtures on human cells. Toxicity modeling, with concentration addition (CA) and independent action (IA) approaches, was performed, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. The results show that UV filter sunscreen constituents and BPs interact at environmentally relevant concentrations. Of notable interest, mixtures containing any pair of three BPs (e.g., BPA + BPS, BPA + BPF and BPS + BPF), together with one sunscreen component (OXYB, 4MBC or EMC), showed strong synergy or overadditive effects. On the other hand, mixtures containing two UV filters (any pair of OXYB, 4MBC and EMC) and one BP (BPA, BPS or BPF) had a strong propensity towards concentration dependent underestimation. The three-component mixtures of UV filters (4MBC, EMC and OXYB) acted in an antagonistic manner toward each other, which was confirmed using a human cell line model. This study is one of the most comprehensive involving sunscreen constituents and BPs in complex mixtures, and provides new insights into potentially important interactions between these compounds.
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| 3. |
- Lagunas-Rangel, Francisco Alejandro, et al.
(författare)
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Role of the synergistic interactions of environmental pollutants in the development of cancer
- 2022
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Ingår i: GeoHealth. - : American Geophysical Union (AGU). - 2471-1403. ; 6:4
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Forskningsöversikt (refereegranskat)abstract
- There is a growing awareness that the large number of environmental pollutants we are exposed to on a daily basis are causing major health problems. Compared to traditional studies that focus on individual pollutants, there are relatively few studies on how pollutants mixtures interact. Several studies have reported a relationship between environmental pollutants and the development of cancer, even when pollutant levels are below toxicity reference values. The possibility of synergistic interactions between different pollutants could explain how even low concentrations can cause major health problems. These intricate that molecular interactions can occur through a wide variety of mechanisms, and our understanding of the physiological effects of mixtures is still limited. The purpose of this paper is to discuss recent reports that address possible synergistic interactions between different types of environmental pollutants that could promote cancer development. Our literature studies suggest that key biological pathways are frequently implicated in such processes. These include increased production of reactive oxygen species, activation by cytochrome P450, and aryl hydrocarbon receptor signaling, among others. We discuss the need to understand individual pathological vulnerability not only in relation to basic genetics and gene expression, but also in terms of measurable exposure to contaminants. We also mention the need for significant improvements in future studies using a multitude of disciplines, such as the development of high-throughput study models, better tools for quantifying pollutants in cancer patients, innovative pharmacological and toxicological studies, and high-efficiency computer analysis, which allow us to analyze the molecular mechanisms of mixtures.Plain Language SummaryIn general, every day we are exposed to many pollutants at the same time, and each pollutant can interact with others in different ways. Notably, two or more pollutants can interact and enhance their effects through a phenomenon called synergy and this would explain why, even at low concentrations, pollutants can have important health effects. Several studies have reported a link between environmental pollutants and cancer. Thus, our review of the literature suggests that synergy phenomena between pollutants can alter key points in cells and facilitate cancer development. Similarly, we mention the complications and needs to assess these complex interactions in subsequent studies.
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| 4. |
- Lagunas-Rangel, Francisco Alejandro, et al.
(författare)
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The potential interaction of environmental pollutants and circadian rhythm regulations that may cause leukemia
- 2022
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Ingår i: Critical reviews in environmental science and technology. - : Informa UK Limited. - 1064-3389 .- 1547-6537. ; 52:22, s. 4094-4112
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Forskningsöversikt (refereegranskat)abstract
- Tumor suppressor genes are highly affected during the development of leukemia, including circadian clock genes. Circadian rhythms constitute an evolutionary molecular machinery involving many genes, such as BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, REV-ERBa, and RORA, for tracking time and optimizing daily life during day-night cycles and seasonal changes. For circulating blood cells many of these genes coordinate their proliferation, output, and function, and therein lies their importance for the development of leukemia. Recent findings suggest that environmental pollutants may affect circadian rhythms and thus affect cancer development and treatment. Such environmental pollutants are often found in mixtures and include benzene, tobacco smoke, pesticides and microplastics. Our understanding of the molecular basis for the interaction mechanisms within complex mixtures is also growing, confirming the plausible occurrence of synergistic (superadditive effect) and antagonistic (cancellation effect) actions of pollutant cocktails. In this work, we discuss the relationship of environmental pollutants and the alteration of circadian rhythms that potentially may cause leukemia. We highlight the need of additional dimensions and perhaps a paradigm shift for future studies in relation to continuously growing magnitude of environmental pollution using multitude of disciplines such as development of high throughput reporter cell lines, other cell screening methods, contaminant measurements in leukemia patients, advanced pharmacology and toxicological measurement of mixtures and highly efficient computer analysis including artificial intelligence, among others.
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| 5. |
- Lax, Cassandra, et al.
(författare)
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The effect of sunscreen 4-methylbenzylidene camphor in different and reproductive models, its bioaccumulation and molecular effects on ligand-receptor interaction, and protein expression
- 2023
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley-Blackwell. - 1742-7835 .- 1742-7843. ; 133:2, s. 130-141
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Forskningsöversikt (refereegranskat)abstract
- 4-Methylbenzylidene camphor (4-MBC) is a photo-absorbing UV filter prevalently used in cosmetics, which can be absorbed into circulation and cause systemic effects. 4-MBC is continued to be released in the environment despite the growing knowledge about its bioaccumulation and endocrine disrupting effects. Previous reviews have mentioned UV-filter together but this review considers 4-MBC alone, due to its prevalence and concerning health effects. This review considers 4-MBC's potential effects on human health regarding systemic and molecular effects, with the main focus on reproduction. Also, the potential bioaccumulation and interactions with receptor systems such as the oestrogen receptors beta and alpha, and progesterone receptor are covered. Additionally, previous studies about 4-MBC's effects on mRNA and protein expression, especially in the prostate and the brain are analysed. Furthermore, 4-MBC is reported to act with inflammatory pathways by activating p38 MAPK and NF-kappa B, leading to the production of inflammatory TNF-alpha and IL-6. 4-MBC was also found to induce apoptosis and inhibit cell proliferation and DNA repair. In conclusion, 4-MBC has wide-ranging effects in many different models interacting with multiple pathways causing long-term effects even at low doses and this knowledge can guide governmental risk assessment, regulation divisions and chemical industries.
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| 6. |
- Liu, Wen, et al.
(författare)
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Dibutyl phthalate disrupts conserved circadian rhythm in Drosophila and human cells
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 783
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Tidskriftsartikel (refereegranskat)abstract
- People are constantly exposed to phthalates, due to their common use in the production of plastics, pharmaceuticals, cosmetics and skin care products. The ability of phthalates to disrupt endocrine signaling, leading to developmental, reproductive and metabolic defects, has been studied, yet how phthalates interfere with these biological functions is still unclear. To uncover DBP interacting molecular pathways, we raised Drosophila melanogaster on food containing dibutyl phthalate (DBP) at various concentrations. Whole transcriptome analysis of adult Drosophila reveals that DBP exposure throughout development disrupts the expression of genes central to circadian rhythm regulation, including increased expression of vrille (vri, human NFIL3), timeless (tim, human TIMELESS) and period (per, human PER3), with decreased expression of Pigment-dispersing factor (Pdf). DBP exposure also alters the expression of the evolutionarily conserved nuclear receptor Hormone receptor-like in 38 (Hr38, human NR4A2), which is known to regulate Pdf expression. Furthermore, behavioral assays determined that exposing Drosophila to DBP throughout development modifies the circadian rhythm of adults. Although DBP inhibits the expression of signaling systems regulating vision, including Rh5 and Rh6, two light-sensing G-protein coupled receptors involved in the daily resetting of circadian rhythm, it does not influence eye development. Circadian rhythm genes are well conserved from flies to humans; therefore, we tested the effect of DBP exposure on human breast cells (MCF10A) and demonstrate that, similar to the fruit fly model, this exposure disrupts circadian rhythm (BMAL1 expression) at doses that promote the proliferation and migration ability of MCF10A cells. Our results are the first to provide comprehensive evidence that DBP interferes with circadian rhythm in both adult Drosophila and human cells, which may help to explain the broad physiological action of phthalates.
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| 7. |
- Lukashina, Nina, et al.
(författare)
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Integrating Statistical and Machine-Learning Approach for Meta-Analysis of Bisphenol A-Exposure Datasets Reveals Effects on Mouse Gene Expression within Pathways of Apoptosis and Cell Survival
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:19
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenols are important environmental pollutants that are extensively studied due to different detrimental effects, while the molecular mechanisms behind these effects are less well understood. Like other environmental pollutants, bisphenols are being tested in various experimental models, creating large expression datasets found in open access storage. The meta-analysis of such datasets is, however, very complicated for various reasons. Here, we developed an integrating statistical and machine-learning model approach for the meta-analysis of bisphenol A (BPA) exposure datasets from different mouse tissues. We constructed three joint datasets following three different strategies for dataset integration: in particular, using all common genes from the datasets, uncorrelated, and not co-expressed genes, respectively. By applying machine learning methods to these datasets, we identified genes whose expression was significantly affected in all of the BPA microanalysis data tested; those involved in the regulation of cell survival include: Tnfr2, Hgf-Met, Agtr1a, Bdkrb2; signaling through Mapk8 (Jnkl)); DNA repair (Hgf-Met, Mgmt); apoptosis (Tmbim6, Bcl2, Apaf1); and cellular junctions (F11r, Cldnd1, Ctnd1 and Yes1). Our results highlight the benefit of combining existing datasets for the integrated analysis of a specific topic when individual datasets are limited in size.
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