Long-Term Exposure of Early-Transformed Human Mammary Cells to Low Doses of Benzo[a]pyrene and/or Bisphenol A Enhances Their Cancerous Phenotype via an AhR/GPR30 Interplay

Donini, Caterina F; Helou, Myriam El; Wierinckx, Anne; Győrffy, Balázs; Aires, Sophie; Escande, Aurélie; Croze, Séverine; Clézardin, Philippe; Lachuer, Joël; Diab‐Assaf, Mona; Ghayad, Sandra E.; Fervers, Béatrice; Cavaillès, Vincent; Maguer-Satta, Véronique; Cohen, Pascale A.

doi:10.3389/fonc.2020.00712

Cited by 14 publications

(14 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BPs might exert their impact on genotoxicity of a carcinogen through modulating CYP enzymes required for its activation. More importantly, the above impact of BP compounds occurred at levels ranging from 0.1 (or 1) to 100 nM, low enough to fall into the range of the real human plasma levels. , This finding appears consistent with a recent report that long-term exposure of early transformed human mammary cells to BaP and BPA at a very low concentration (0.1 nM) synergistically enhanced their cancerous phenotype via an AhR/G protein-coupled receptor 30 . Moreover, human exposure to BPs is not limited to a single BP compound, while multiple BPs may be present in human bodies; thus, combined effects of BPs, such as BPA, BPF, BPS, and BPAF may lead to amplified effect of BPs.…”

Section: Resultssupporting

confidence: 88%

“…14,69 This finding appears consistent with a recent report that long-term exposure of early transformed human mammary cells to BaP and BPA at a very low concentration (0.1 nM) synergistically enhanced their cancerous phenotype via an AhR/G protein-coupled receptor 30. 70 Moreover, human exposure to BPs is not limited to a single BP compound, while multiple BPs may be present in human bodies; 15 thus, combined effects of BPs, such as BPA, BPF, BPS, and BPAF may lead to amplified effect of BPs. An example for such behavior is the additive induction of AhR and CYP1A1 in HepG2 cells by a mixture of BPs.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Song

et al. 2021

Environ. Sci. Technol.

View full text Add to dashboard Cite

Bisphenol (BP) compounds are endocrine-disrupting organic pollutants. BPs may increase the messenger RNA (mRNA) transcripts of nuclear receptors (NRs) regulating the expression of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes. Their impact on the genotoxicity of metabolically activated carcinogens, however, remains unknown. In this study, effects of the bisphenols A, F, S, and AF on the expression of the aryl hydrocarbon receptor (AhR), the pregnane X receptor (PXR), the constitutive androstane receptor, and individual xenobiotic-metabolizing CYP enzymes in a human hepatoma (HepG2) cell line were investigated, along with in silico binding studies of BPs to each receptor. The results indicated that each BP at 1 to 100 nM concentrations increased the mRNA transcripts and protein levels of AhR, PXR, CYP1A1, 1A2, 1B1, 2E1, and 3A4. The predicted affinities of the BPs for binding AhR were comparable to those of potent agonists. Pretreatment of HepG2 cells with each BP potentiated the induction of micronuclei by benzo[a]pyrene, aflatoxin B1, benzene, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; this effect was abolished/reduced by inhibitors of NRs and/or CYPs. Our study suggests that BPs at human exposure levels may aggravate chromosome damage by several impactful carcinogens in human cells by inducing relevant CYP enzymes, mostly via NR modulation.

show abstract

Section: Resultssupporting

confidence: 88%

Section: ■ Results and Discussionmentioning

confidence: 99%

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Song

et al. 2021

Environ. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that some nuclear receptors are target genes of BPA, such as androgen receptor 45 (AR), estrogen receptor 1 (ESR1), estrogen receptor 2 46 (ESR2), and aryl hydrocarbon receptor 47 (AHR). In our results, all of the aforementioned four genes were predicted as top 100 interactive genes for BPA.…”

Section: Discussionmentioning

confidence: 99%

“…BPA belongs to the endocrine disrupting class of chemicals, and low dose BPA can impact reproduction, the immune system, and is related to hormone-dependent cancers 22 . Previous studies have shown that some nuclear receptors are target genes of BPA, such as androgen receptor 28 ( AR ), estrogen receptor 1 ( ESR1 ), estrogen receptor 2 29 ( ESR2 ), and aryl hydrocarbon receptor 30 ( AHR ). In our results, all of the aforementioned four genes were predicted as top 100 interactive genes for BPA.…”

Section: Discussionmentioning

confidence: 99%

Data Fusion by Matrix Completion for Exposome Target Interaction Prediction

Wang

Kim

Bagherian

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Exposure to toxic chemicals presents a huge health burden and disease risk. Key to understanding which chemicals cause specific toxic effects is determining the molecular target(s) of these chemicals. Given that over a thousand new chemicals are produced annually, it is infeasible to perform a comprehensive safety assessment for all novel chemicals due to limited resources. Thus, a robust computational method for discovering targets of environmental exposures, which can then be used to prioritize chemicals for further study, is a promising direction for public health research. Objectives: We implemented a novel matrix completion algorithm named coupled matrix-matrix completion (CMMC) for predicting exposome-target interactions. Methods: The low rank matrix completion problem can be described as predicting missing values of an incomplete un-observed/under-observed or partially observed matrix. Different from previous matrix completion algorithms based on matrix factorization, the CMMC algorithm incorporates two coupled matrices in form of auxiliary information to help better optimize the distance metric and maintains a fast runtime. The present data fusion model has the potential to automatically reveal shared and unshared components through modeling constraints. The two coupled matrices represent the relationships among the chemical exposures and gene targets, respectively, and help jointly analyze incomplete data sets. We collected and processed relevant data from the Comparative Toxicogenomics Database (CTD) as a benchmark dataset for implementing and testing our method and comparing it to alternative prediction methods. Results: Our method achieved an AUC of 0.89 on the benchmark dataset generated in this study. Compared to other state-of-the-art methods, CMMC achieved the best performance for predicting environmental chemical-gene target interactions. The case study shows that CMMC can be used to discover potential molecular targets of novel chemicals without any prior bioactivity knowledge. Discussion: Our CMMC approach is a powerful method for predicting the target genes of environmental exposures.

show abstract

“…These include in vitro ERα-mediated effects of BPA and its analogues on the upregulation of genes involved in cell growth, migration, invasion and cancer development [139], and low doses BPA-induced phosphorylation of its functional non-genomic target Protein Kinase D1 (PKD1), which mediates cell proliferation and anchorage-independent growth in BC cells [140]. Moreover, BPA oncogenic potential regarding BC is also found in its ability to enhance GPER-induced cancerous phenotype [141] and focal adhesion assembly through focal adhesion kinase (FAK), Src and ERK2 in a triple-negative BC model [142]. Others have shown that exposure to xenoestrogens like BPA can increase adult prostate size and induce PC [143].…”

Section: Bisphenolsmentioning

confidence: 99%

Endocrine-Disrupting Chemicals’ (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1

Buoso

Masi

Racchi

et al. 2020

IJMS

View full text Add to dashboard Cite

Endocrine disruptors (EDCs) can display estrogenic and androgenic effects, and their exposure has been linked to increased cancer risk. EDCs have been shown to directly affect cancer cell regulation and progression, but their influence on tumour microenvironment is still not completely elucidated. In this context, the signalling hub protein RACK1 (Receptor for Activated C Kinase 1) could represent a nexus between cancer and the immune system due to its roles in cancer progression and innate immune activation. Since RACK1 is a relevant EDCs target that responds to steroid-active compounds, it could be considered a molecular bridge between the endocrine-regulated tumour microenvironment and the innate immune system. We provide an analysis of immunomodulatory and cancer-promoting effects of different EDCs in shaping tumour microenvironment, with a final focus on the scaffold protein RACK1 as a pivotal molecular player due to its dual role in immune and cancer contexts.

show abstract

Long-Term Exposure of Early-Transformed Human Mammary Cells to Low Doses of Benzo[a]pyrene and/or Bisphenol A Enhances Their Cancerous Phenotype via an AhR/GPR30 Interplay

Cited by 14 publications

References 86 publications

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Data Fusion by Matrix Completion for Exposome Target Interaction Prediction

Endocrine-Disrupting Chemicals’ (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1

Contact Info

Product

Resources

About