Carcinogenic risk and Bisphenol A exposure: A focus on molecular aspects in endoderm derived glands

Cuomo, Danila; Porreca, Immacolata; Cobellis, Gilda; Tarallo, Roberta; Nassa, Giovanni; Falco, Geppino; Nardone, Antonio; Rizzo, Francesca; Mallardo, Massimo; Ambrosino, Concetta

doi:10.1016/j.mce.2017.01.027

Cited by 34 publications

(15 citation statements)

References 235 publications

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“…This has raised concerns among regulatory agencies all over the world [57]. Based on this, the United States Environmental Protection Agency (EPA) has determined a reference dose for BPA of 50 μg/kg body weight/day whereas the European Food Safety Authority (EFSA) have determined a reference dose of 4 μg/kg body weight/day [62]. In vitro, BPA has been found to cause mutagenicity in human RSa cells (a human embryonic clonal cell line established by double infection with Rous sarcoma virus and Simian virus 40) and HeLa cells [63] within the range of 100 nM to 10 μM [64].…”

Section: Bisphenol Amentioning

confidence: 99%

“…In vitro, BPA has been found to cause mutagenicity in human RSa cells (a human embryonic clonal cell line established by double infection with Rous sarcoma virus and Simian virus 40) and HeLa cells [63] within the range of 100 nM to 10 μM [64]. Even though a direct genotoxic effect of BPA at low doses has not been reported, exposure to BPA at environmentally relevant doses, primarily during the developmental stages, represents a risk for carcinogenesis [62]. This compound has therefore become an environmental contaminant of considerable interest [49].…”

Section: Bisphenol Amentioning

confidence: 99%

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Bisphenol a and mesenchymal stem cells: Recent insights

et al. 2018

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Mesenchymal stem cells (MSCs) are found in all adult mesenchymal tissues. They play a role in the maintenance of tissue homeostasis and repair by allowing renewal of the cellular stock. MSCs can be isolated from both human and animal sources. These cells are important in regenerative medicine and cell therapy, thus adipose tissue is a rich and promising source of these cells. Adipose-derived stem cells (ASCs) are often effective and safe, and have been used in preclinical and clinical studies for both autologous and allogeneic transplantation. The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs provides an important alternative therapeutic solution for the treatment of many diseases. However, it is necessary to have control of the cell manipulation process prior to their use. Exposure of humans to the endocrine disruptor bisphenol A (BPA) has been associated with increased weight and obesity, but the mechanisms by which BPA increases adipose tissue in humans remains to be determined. BPA has been classified as a potent endocrine-disrupting chemical that interferes with adipogenesis. Currently, few studies have reported the effect of BPA on the integrity and capacity for differentiation of MSCs. Thus, this review aims to present, for the first time, a current survey and a discussion of the effects of BPA action on MSCs.

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Section: Bisphenol Amentioning

confidence: 99%

Section: Bisphenol Amentioning

confidence: 99%

Bisphenol a and mesenchymal stem cells: Recent insights

et al. 2018

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“…This is because BPA is commonly used in the production of plastics and it is a component of various everyday objects, such as bottles, food containers and cans, paints, thermal paper, elements of cars and furniture, household goods, and many other things. BPA can flush out from the above mentioned things, penetrate into the food, water, soil, and air, and then get into living organisms by the gastrointestinal tract, skin, or lungs [ 18 ]. Due to the similarity to estrogen and the possibility of estrogen receptor stimulation, BPA is identified as an endocrine disruptor [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

Rytel

2018

IJMS

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Bisphenol A (BPA), a substance commonly used in the manufacture of plastics, shows multidirectional negative effects on humans and animals. Due to similarities to estrogens, BPA initially leads to disorders in the reproductive system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active substance which enhances the survivability of cells, inhibits apoptosis, and protects tissues against damaging factors. Because the influence of BPA on the nervous system has also been described, the aim of the present study was to investigate for the first time the influence of various doses of BPA on neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus using the routine single- and double-immunofluorescence technique. The obtained results have shown that BPA increases the number and affects the neurochemical characterization of NRG-1-LI in the uterus, and changes are visible even under the impact of small doses of this toxin. The character of observed changes depended on the dose of BPA and the part of the uterus studied. These observations suggest that NRG-1 in nerves supplying the uterus may play roles in adaptive and protective mechanisms under the impact of BPA.

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“…The reported data partially fulfil this gap, firstly investigating the CPF effects on immortalized rat thyrocytes [32] and identifying the gene-network associated with hepatocellular carcinoma further validated in other in vitro and in vivo model of thyroid cancers. We applied this gene network to thyroid cancers considering that: (i) IPA analysis refers to published results to build up the prediction and liver dysfunctions/carcinogenesis are widely investigated; (ii) we have recently proposed that organs of similar developmental origin might share common mechanisms of environmental carcinogenesis [26]; and (iii) liver shares the same developmental origin with thyroid. Despite the discrepancies in their regulation, the transcripts/proteins included in the ECGS or in the bioinformatically built ECGN were indeed altered in thyroid carcinogenesis in vitro (FRTL-5-RasV12 and FRTL-5 exposed to TCDD and CPF) and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Similar results came out from a study on FRTL-5, immortalized rat thyrocytes, exposed to BPA. Starting from these observations, we proposed that mechanisms of toxicity can be similar in organ shearing the developmental origin [26]. Since thyroid and liver are both derived from endoderm, we chose some of the genes potentially involved in liver carcinogenesis as components of a signature that might be applied to other endodermal organs, herein defined endodermal carcinogenic gene-network (ECGN).…”

Section: Introductionmentioning

confidence: 99%

A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis

Reale

Russo

Credendino

et al. 2019

IJERPH

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Epidemiological and experimental studies emphasize the link between environmental chemicals exposure and thyroid cancer. However, this association is strongly debated and the mechanisms of action of environmental thyroid carcinogens still need to be identified. The analysis of in vitro transcriptomic data developed to investigate the effects of chlorpyrifos on immortalized thyrocytes highlighted the impaired expression of genes involved in endodermal carcinogenesis. This endodermal carcinogenic gene-network (ECGN, including Zfp36l2, Dmbt1, Ddit4), was validated in cellular and mouse models of thyroid carcinogenesis, characterized by the constitutive activation of the mitogen-activated protein kinase (MAPK) pathway and in immortalized thyrocytes exposed to tetrachlorodibenzo-p-dioxin (TCDD) and chlorpyrifos (CPF). The mRNA levels of Zfp36l2, Dmbt1 and Ddit4 were increased in models characterized by MAPK activation or following TCDD exposure, whereas they were inhibited by CPF exposure. Overall, the ECGN transcripts identify a novel gene-regulatory network associated with thyroid carcinogenesis promoted by genetic mutation or by environmental carcinogens. The latter have opposite effects on the modulation of the ECGN transcripts according to their mechanisms of action in promoting carcinogenesis. Therefore, the analyses of ECGN might be helpful in discriminating compounds that promote cellular survival associated or not to proliferation of thyrocytes.

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Carcinogenic risk and Bisphenol A exposure: A focus on molecular aspects in endoderm derived glands

Cited by 34 publications

References 235 publications

Bisphenol a and mesenchymal stem cells: Recent insights

Bisphenol a and mesenchymal stem cells: Recent insights

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis

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