Environmental contaminant BPA causes intestinal damage by disrupting cellular repair and injury homeostasis in vivo and in vitro

Wang, Kai; Qiu, Lei; Zhu, Junjia; Sun, Qi; Qu, Wei; Yu, Yifeng; Zhao, Zhenguo; Shao, Guoqiang

doi:10.1016/j.biopha.2021.111270

Cited by 27 publications

(14 citation statements)

References 48 publications

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“…We found that BPA was toxic to both colon cancer cells and normal colon epithelial cells, which is consistent with the literature [ 14 , 15 , 22 ]. Wang et al showed that dietary BPA induced apoptosis and mitochondrial dysfunction in mouse colon and liver [ 14 ].…”

Section: Discussionsupporting

confidence: 93%

“…BPA predisposes intestinal epithelial cells to oxidative stress by increasing reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as by decreasing the activity of antioxidant enzymes (SOD, GPx, CAT, and T-AOC). Moreover, BPA induces inflammatory responses via multiple mechanisms including upregulating the key factors of the innate immune system (TLR2, TLR4, MyD88, and NF-κB) and secreting pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) [ 15 ]. BPA and its substitute, fluorene-9-bisphenol (BHPF), induced significant alterations in gut metabolites associated with the inflammatory response in a dextran sulfate sodium-induced colitis mouse model [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A

Nair

Malhab

Abdel‐Rahman

2022

IJMS

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Colorectal cancer is a common cancer with a poor prognosis in both males and females. The influence of bisphenol A (BPA), a widely used environmental contaminant, in colon cancer development and progression is not well identified, in spite of the fact that the most common mode of exposure to BPA is ingestion. The aim of this work is to elucidate the carcinogenic effects of BPA in the colon in vitro. We analyzed BPA’s effects on human colon epithelial (HCoEpiC) and colon cancer (HCT116) cells. BPA exerted cytotoxic effects and augmented the 5FU cytotoxicity on both cell lines at high doses, while it did not show this effect at low doses. Therefore, we focused on studying the effects of low-dose (0.0043 nM) exposure on normal colonic epithelial cells for a long period of time (two months), which is more consistent with environmental exposure levels and patterns. BPA increased cellular invasiveness through collagen and the ability to anchorage-independent cell growth, as measured by colony formation in soft agar, which could support oncogenicity. To gain insights into the mechanism of these actions, we performed transcriptomic analysis using next-generation sequencing, which revealed 340 differentially expressed transcripts by BPA in HCT116 and 75 in HCoEpiC. These transcripts belong in many cancer-related pathways such as apoptosis, cell proliferation, signal transduction, and angiogenesis. Some of the significant genes (FAM83H, CXCL12, PITPNA, HMOX1, DGKZ, NR5A2, VMP1, and ID1) were confirmed by quantitative RT-PCR. Furthermore, BPA induced the phosphorylation of protein kinases such as JNK1/2/3, GSK-3α/β, AMPKα1, AKT1/2/3, AMPKα2, HSP27, β-catenin, STAT2, Hck, Chk2, FAK, and PRAS40 in HCoEpiC, as well as GSK-3α/β, p53, AKT1/2/3, p70 S6 kinase, and WNK1 in HCT116. The majority of these proteins are involved in potential carcinogenic pathways. Taken together, these data suggest that BPA plays a role in colon carcinogenesis, and they provide insights into the molecular mechanisms of colon epithelial cell transformation by BPA. Increasing exposure to environmental toxins such as BPA can explain the increasing incidence of colorectal cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A

Nair

Malhab

Abdel‐Rahman

2022

IJMS

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“…Firstly, the cross-sectional study design does not allow us to draw causal conclusions. Secondly, previous studies showed that other persistent chemicals like polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs) and bisphenols are also associated with cytokines 28 , 39 . It remains to be tested whether our finding is due to such unmeasured confounding.…”

Section: Discussionmentioning

confidence: 99%

Emerging and legacy PFAS and cytokine homeostasis in women of childbearing age

Nian

Zhou

Feng

et al. 2022

Sci Rep

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Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals. Legacy PFAS have been phased out of production in most developed countries and emerging PFAS (short-chain PFAS and polyfluorinated compounds) are used as legacy PFAS alternatives. The effect of legacy and emerging PFAS on cytokine homeostasis in human remains poorly understood. This study aimed to evaluate the associations between legacy and emerging PFAS and cytokine profiles, and identify the main contributors to the disturbance of cytokine homeostasis. We quantified 21 PFAS in 198 Chinese women of childbearing age from 2015 to 2016. 13 cytokines were measured using the Meso Scale Discovery U-PLEX and V-PLEX platforms. The associations between PFAS exposure and cytokine levels were assessed using multiple linear regression (single-exposure), and Bayesian kernel machine regression (BKMR) models (PFAS mixture exposure). In single PFAS models, legacy and alternative PFAS were positively associated with Th1 and Treg cytokines, and negatively associated with Th2 and Th17 cytokines. For instance, each ln-unit increase in 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) was associated with a decrease in IL-10 by − 0.228 (95% CI: − 0.336, − 0.120), − 0.153 (95% CI: − 0.277, − 0.030), and − 0.174 (95% CI: − 0.339, − 0.010), respectively. The BKMR model showed a significantly positive association of PFAS mixture with TGF-β and a negative association with IL-10. Overall, these results indicate that both legacy and emerging PFAS may affect the homeostasis of cytokines.

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“…EGFR, linked to the erythroblastic leukemia viral oncogene signaling pathway, is the receptor for epidermal growth factor and TGF-α, among others, and thus stimulates cell growth while inhibiting apoptosis, which is why it is also considered as an oncogene [ 64 ]. In a murine and intestinal epithelial cell model, the transcriptional activity of NF-κB, production of inflammatory cytokines, as well as apoptotic processes were promoted by BPA, explaining the risk for BPA-induced gut injury [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines

Oldenburg

Fürhacker

Hartmann

et al. 2021

Environmental Epigenetics

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4,4ʹ-Isopropylidenediphenol (bisphenol A, BPA), a chemical substance that is widely used mainly as a monomer in the production of polycarbonates, in epoxy resins, and in thermal papers, is suspected to cause epigenetic modifications with potentially toxic consequences. Due to its negative health effects, BPA is banned in several products and is replaced by other bisphenols such as bisphenol S and bisphenol F. The present study examined the effects of BPA, bisphenol S, bisphenol F, p,pʹ-oxybisphenol, and the BPA metabolite BPA β-d-glucuronide on the expression of a set of microRNAs (miRNAs) as well as long interspersed nuclear element-1 methylation in human lung fibroblast and Caco-2 cells. The results demonstrated a significant modulation of the expression of different miRNAs in both cell lines including miR-24, miR-155, miR-21, and miR-146a, known for their regulatory functions of cell cycle, metabolism, and inflammation. At concentrations between 0.001 and 10 µg/ml, especially the data of miR-155 and miR-24 displayed non-monotonous and often significant dose–response curves that were U- or bell-shaped for different substances. Additionally, BPA β-d-glucuronide also exerted significant changes in the miRNA expression. miRNA prediction analysis indicated effects on multiple molecular pathways with relevance for toxicity. Besides, long interspersed nuclear element-1 methylation, a marker for the global DNA methylation status, was significantly modulated by two concentrations of BPA and p,pʹ-oxybisphenol. This pilot study suggests that various bisphenols, including BPA β-d-glucuronide, affect epigenetic mechanisms, especially miRNAs. These results should stimulate extended toxicological studies of multiple bisphenols and a potential use of miRNAs as markers.

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Environmental contaminant BPA causes intestinal damage by disrupting cellular repair and injury homeostasis in vivo and in vitro

Cited by 27 publications

References 48 publications

Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A

Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A

Emerging and legacy PFAS and cytokine homeostasis in women of childbearing age

Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines

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