DNA damage and methylation induced by organophosphate flame retardants: Tris(2-chloroethyl) phosphate and tris(1-chloro-2-propyl) phosphate in human peripheral blood mononuclear cells

Bukowski, Karol; Wysokiński, Daniel; Mokra, Katarzyna; Woźniak, Katarzyna

doi:10.1177/0960327119839174

Cited by 16 publications

(3 citation statements)

References 32 publications

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“…2 C and D). Previously, it has been recognized that elevated concentrations of TCEP may have the potential to induce DNA strand breaks and elevate oxidative stress, ultimately leading to cellular apoptosis [ 37 ]. Therefore, we designated 1 mM TCEP as the optimal dose for breaking disulfide bonds without interfering with cell viability.…”

Section: Resultsmentioning

confidence: 99%

Cell Surface Modification-Mediated Primary Intestinal Epithelial Cell Culture Platforms for Assessing Host–Microbiota Interactions

Sittipo,

Anggradita,

Kim

et al. 2024

Biomater Res

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Background: Intestinal epithelial cells (IECs) play a crucial role in regulating the symbiotic relationship between the host and the gut microbiota, thereby allowing them to modulate barrier function, mucus production, and aberrant inflammation. Despite their importance, establishing an effective ex vivo culture method for supporting the prolonged survival and function of primary IECs remains challenging. Here, we aim to develop a novel strategy to support the long-term survival and function of primary IECs in response to gut microbiota by employing mild reduction of disulfides on the IEC surface proteins with tris(2-carboxyethyl)phosphine. Methods: Recognizing the crucial role of fibroblast-IEC crosstalk, we employed a cell surface modification strategy, establishing layer-to-layer contacts between fibroblasts and IECs. This involved combining negatively charged chondroitin sulfate on cell surfaces with a positively charged chitosan thin film between cells, enabling direct intercellular transfer. Validation included assessments of cell viability, efficiency of dye transfer, and IEC function upon lipopolysaccharide (LPS) treatment. Results: Our findings revealed that the layer-by-layer co-culture platform effectively facilitates the transfer of small molecules through gap junctions, providing vital support for the viability and function of primary IECs from both the small intestine and colon for up to 5 days, as evident by the expression of E-cadherin and Villin. Upon LPS treatment, these IECs exhibited a down-regulation of Villin and tight junction genes, such as E-cadherin and Zonula Occludens-1 , when compared to their nontreated counterparts. Furthermore, the transcription level of Lysozyme exhibited an increase, while Mucin 2 showed a decrease in response to LPS, indicating responsiveness to bacterial molecules. Conclusions: Our study provides a layer-by-layer-based co-culture platform to support the prolonged survival of primary IECs and their features, which is important for understanding IEC function in response to the gut microbiota.

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Section: Resultsmentioning

confidence: 99%

Cell Surface Modification-Mediated Primary Intestinal Epithelial Cell Culture Platforms for Assessing Host–Microbiota Interactions

Sittipo,

Anggradita,

Kim

et al. 2024

Biomater Res

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“…Under alkaline conditions, the broken DNA is electrostretched from the nuclei head, forming a comet tail that can be measured as DNA damage in cells. DNA damage in HepG2 cells was examined by a previously described method [ 53 , 54 ]. TDCPP-exposed cells (100–400 µM, 3 days) were trypsinized and washed twice with PBS at 3000 rpm for 3 min.…”

Section: Methodsmentioning

confidence: 99%

Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells

Saquib

Alsalem

Siddiqui

et al. 2022

Cells

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Tris(1,3-Dichloro-2-propyl)phosphate (TDCPP) is an organophosphorus flame retardant (OPFR) widely used in a variety of consumer products (plastics, furniture, paints, foams, and electronics). Scientific evidence has affirmed the toxicological effects of TDCPP in in vitro and in vivo test models; however, its genotoxicity and carcinogenic effects in human cells are still obscure. Herein, we present genotoxic and carcinogenic properties of TDCPP in human liver cells (HepG2). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and neutral red uptake (NRU) assays demonstrated survival reduction in HepG2 cells after 3 days of exposure at higher concentrations (100–400 μM) of TDCPP. Comet assay and flow cytometric cell cycle experiments showed DNA damage and apoptosis in HepG2 cells after 3 days of TDCPP exposure. TDCPP treatment incremented the intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca2+ influx, and esterase level in exposed cells. HepG2 mitochondrial membrane potential (ΔΨm) significantly declined and cytoplasmic localization of P53, caspase 3, and caspase 9 increased after TDCPP exposure. qPCR array quantification of the human cancer pathway revealed the upregulation of 11 genes and downregulation of two genes in TDCPP-exposed HepG2 cells. Overall, this is the first study to explicitly validate the fact that TDCPP bears the genotoxic, hepatotoxic, and carcinogenic potential, which may jeopardize human health.

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“…DNA methylation is the most studied epigenetic regulator in relation to environmental exposures and xenobiotic toxicity. DNA methylation has been analyzed in terms of the effect of glyphosate [27] and its metabolite-aminomethylphosphonic acid (AMPA) [28], phosphorus flame retardants [29], aflatoxin B1, bisphenol A, air pollutants, persistent organic pollutants, arsenic, cadmium, chromium, lead, mercury, tobacco smoke, nutritional factors or BaP [30].…”

Section: Epigenetic Changes and Factors Regulating Themmentioning

confidence: 99%

Influence of Benzo(a)pyrene on Different Epigenetic Processes

Bukowska

Sicińska

2021

IJMS

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Epigenetic changes constitute one of the processes that is involved in the mechanisms of carcinogenicity. They include dysregulation of DNA methylation processes, disruption of post-translational patterns of histone modifications, and changes in the composition and/or organization of chromatin. Benzo(a)pyrene (BaP) influences DNA methylation and, depending on its concentrations, as well as the type of cell, tissue and organism it causes hypomethylation or hypermethylation. Moreover, the exposure to polyaromatic hydrocarbons (PAHs), including BaP in tobacco smoke results in an altered methylation status of the offsprings. Researches have indicated a potential relationship between toxicity of BaP and deregulation of the biotin homeostasis pathway that plays an important role in the process of carcinogenesis. Animal studies have shown that parental-induced BaP toxicity can be passed on to the F1 generation as studied on marine medaka (Oryzias melastigma), and the underlying mechanism is likely related to a disturbance in the circadian rhythm. In addition, ancestral exposure of fish to BaP may cause intergenerational osteotoxicity in non-exposed F3 offsprings. Epidemiological studies of lung cancer have indicated that exposure to BaP is associated with changes in methylation levels at 15 CpG; therefore, changes in DNA methylation may be considered as potential mediators of BaP-induced lung cancer. The mechanism of epigenetic changes induced by BaP are mainly due to the formation of CpG-BPDE adducts, between metabolite of BaP—BPDE and CpG, which leads to changes in the level of 5-methylcytosine. BaP also acts through inhibition of DNA methyltransferases activity, as well as by increasing histone deacetylases HDACs, i.e., HDAC2 and HDAC3 activity. The aim of this review is to discuss the mechanism of the epigenetic action of BaP on the basis of the latest publications.

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DNA damage and methylation induced by organophosphate flame retardants: Tris(2-chloroethyl) phosphate and tris(1-chloro-2-propyl) phosphate in human peripheral blood mononuclear cells

Cited by 16 publications

References 32 publications

Cell Surface Modification-Mediated Primary Intestinal Epithelial Cell Culture Platforms for Assessing Host–Microbiota Interactions

Cell Surface Modification-Mediated Primary Intestinal Epithelial Cell Culture Platforms for Assessing Host–Microbiota Interactions

Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells

Influence of Benzo(a)pyrene on Different Epigenetic Processes

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