Co-exposure to BPA and DEHP enhances susceptibility of mammary tumors via up-regulating Esr1/HDAC6 pathway in female rats

Zhang, Xuan; Cheng, Cheng; Zhang, Guopei; Xiao, Mingyang; Li, Liuli; Wu, Shengwen; Lu, Xiaobo

doi:10.1016/j.ecoenv.2021.112453

Cited by 28 publications

(8 citation statements)

References 38 publications

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“…The mass production and wide application of BPA seriously affect human beings’ health and threaten the abundance of environmental species. BPA can increase the incidence and susceptibility of various cancers, including breast, ovary, prostate, and even colon cancer ( 7 , 19 ). Low doses of BPA cause resistance to classical chemotherapeutics in multiple types of cancer cells ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Bisphenol A Promotes the Progression of Colon Cancer Through Dual-Targeting of NADPH Oxidase and Mitochondrial Electron-Transport Chain to Produce ROS and Activating HIF-1α/VEGF/PI3K/AKT Axis

et al. 2022

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Bisphenol A (BPA) is a high-production-volume industrial chemical. Despite recent research conducted on its carcinogenicity, its role in the development of colon cancer (CC) has been rarely studied. This study aims to evaluate the effects of BPA on the migration and invasion of CC cells. First, we clinically verified that patients with CC exhibit higher serum BPA level than healthy donors. Subsequently, different CC cell lines were exposed to a series of BPA concentrations, and the migration and invasion of cells were detected by the wound healing test and transwell assay. Finally, N-acetyl-L-cysteine (NAC) and siHIF-1α intervention was used to explore the effects of ROS and HIF-1α on cell migration and invasion, respectively. The results demonstrated that the occurrence of BPA-induced migration and invasion were dependent on the dose and time and was most pronounced in DLD1 cells. ROS production was jointly driven by NADPH oxidase (NOX) and mitochondrial electron-transport chain (ETC). Furthermore, the intervention of NAC and siHIF-1α blocked the HIF-1α/VEGF/PI3K/AKT axis and inhibited cell migration and invasion. In conclusion, our results suggest that BPA exposure promotes the excessive production of ROS induced by NOX and ETC, which in turn activates the HIF-1α/VEGF/PI3K/AKT axis to promote the migration and invasion of CC cells. This study provides new insights into the carcinogenic effects of BPA on CC and warns people to pay attention to environmental pollution and the harm caused to human health by low-dose BPA.

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Section: Discussionmentioning

confidence: 99%

Bisphenol A Promotes the Progression of Colon Cancer Through Dual-Targeting of NADPH Oxidase and Mitochondrial Electron-Transport Chain to Produce ROS and Activating HIF-1α/VEGF/PI3K/AKT Axis

et al. 2022

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“…Another interesting aspect of this study is the evaluation of co-exposure to DEHP and BPA in women; indeed, the concentrations of these plasticizers were positively correlated, in particular in Central and Southern Italy, suggesting possible common sources or an extensive use of plastics, resulting in a consequent cumulative exposure. This evidence is particularly relevant, considering the effects exerted by the mixture on the glucose metabolism, thyroid and cancer development exerted by the mixture and shown in in vivo studies (Baralic et al, 2021; Lin et al, 2011; Zhang et al, 2021; Zhang et al, 2022). In addition, the combined exposure of juvenile rats to DEHP and BPA, at same doses recorded in this HBM study, was associated to synergic action in the metabolic system and antagonism action in the reproductive and endocrine systems (Tassinari et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Women exposure to Di(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA) from different residing areas in Italy: data from the LIFE PERSUADED project

Carli

Tait

Busani

et al. 2022

Preprint

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Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors. In the frame of the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di (2-ethylhexyl) phthalate (DEHP) metabolites in 900 Italian women enrolled between 2015 and 2017 and living in North, Centre and South of Italy in both rural and urban areas. The whole cohort, representative of the Italian female adult population, was exposed to DEHP and BPA with measurable levels above the limit of detection (LOD) in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in South compared to Central and Northern Italy and for BPA in Northern compared to Central and Southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 μg/kg per day, about 36-fold below the current temporary Tolerable Daily Intake of 4 μg/kg per day established by the European Food Safety Authority in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. These results suggest to further limit the exposure to DEHP and BPA through specific legislative measures.

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“…There is also ongoing research on the effects of endocrine disruptors on the transcriptional control of morphogenetic processes in endocrine organs [ 62 , 63 ].…”

Section: Studies On the Effects Of Low Doses Of Ddt On The Adrenal Glandsmentioning

confidence: 99%

Dichlorodiphenyltrichloroethane and the Adrenal Gland: From Toxicity to Endocrine Disruption

Timokhina

Yaglov

Назимова

2021

Toxics

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Endocrine disruptors are exogenous compounds that pollute the environment and have effects similar to hormones when inside the body. One of the most widespread endocrine disruptors in the wild is the pesticide dichlorodiphenyltrichloroethane (DDT). Toxic doses of DDT are known to cause cell atrophy and degeneration in the adrenal zona fasciculata and zona reticularis. Daily exposure in a developing organism to supposedly non-toxic doses of DDT have been found to impair the morphogenesis of both the cortex and the medulla of the adrenal glands, as well as disturbing the secretion of hormones in cortical and chromaffin cells. Comparison of high and very low levels of DDT exposure revealed drastic differences in the morphological and functional changes in the adrenal cortex. Moreover, the three adrenocortical zones have different levels of sensitivity to the disruptive actions of DDT. The zona glomerulosa and zona reticularis demonstrate sensitivity to both high and very low levels of DDT in prenatal and postnatal periods. In contrast, the zona fasciculata is less damaged by low (supposedly non-toxic) exposure to DDT and its metabolites but is affected by toxic levels of exposure; thus, DDT exerts both toxic and disruptive effects on the adrenal glands, and sensitivity to these two types of action varies in adrenocortical zones. Disruptive low-dose exposure leads to more severe affection of the adrenal function.

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Co-exposure to BPA and DEHP enhances susceptibility of mammary tumors via up-regulating Esr1/HDAC6 pathway in female rats

Cited by 28 publications

References 38 publications

Bisphenol A Promotes the Progression of Colon Cancer Through Dual-Targeting of NADPH Oxidase and Mitochondrial Electron-Transport Chain to Produce ROS and Activating HIF-1α/VEGF/PI3K/AKT Axis

Bisphenol A Promotes the Progression of Colon Cancer Through Dual-Targeting of NADPH Oxidase and Mitochondrial Electron-Transport Chain to Produce ROS and Activating HIF-1α/VEGF/PI3K/AKT Axis

Women exposure to Di(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA) from different residing areas in Italy: data from the LIFE PERSUADED project

Dichlorodiphenyltrichloroethane and the Adrenal Gland: From Toxicity to Endocrine Disruption

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