Effects of human blood levels of two PAH mixtures on the AHR signalling activation pathway and CYP1A1 and COMT target genes in granulosa non-tumor and granulosa tumor cell lines

Zajda, Karolina; Ptak, Anna; Rak, Agnieszka; Fiedor, Elżbieta; Grochowalski, Adam; Milewicz, Tomasz; Gregoraszczuk, Ewa Ł.

doi:10.1016/j.tox.2017.07.003

Cited by 36 publications

(16 citation statements)

References 53 publications

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“…Cells in basal and FSH-stimulated cultures were exposed to two different mixtures: mixture 1 (M1) in the amount of 276.2 ng/ml, composed of all 16 priority PAHs: naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benz(a)anthracene, chrysene, benzo(a)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, indeno(1,2,3-cd)pyrene, dibenzo(ah)anthracene and benzo(ghi)perylene at the levels observed in human blood: 45.5 ± 4.5, 1.45 ± 0.15, 0.9 ± 0.0, 6.25 ± 3.75, 37.95 ± 3.2, 58.1 ± 5.5, 50.5 ± 6.0, 33.0 ± 1.05, 16.25 ± 9.75, 5.05 ± 1.05, 2.3 ± 0.4, 2.45 ± 0.75, 1.6 ± 0.5, 4.7 ± 0.85, 5.15 ± 0.0 and 5.05 ± 1.9 ng/ml, respectively; and mixture 2 (M2) in the amount of 183.2 ng/ml, composed of naphthalene, phenanthrene, anthracene, fluoranthene and pyrene; these five compounds were found in the highest amounts in maternal and umbilical cord blood, collected from 20 women during delivery and were determined in a previous study. 17 A stock solution of mixtures containing 16 or 5 weight amounts of PAH, respectively, were dissolved in methanol. The final concentration of methanol in the medium did not exceed 0.1%.…”

Section: Methodsmentioning

confidence: 99%

Environmental polycyclic aromatic hydrocarbons mixture, in human blood levels, decreased oestradiol secretion by granulosa cells via ESR1 and GPER1 but not ESR2 receptor

Zajda

Gregoraszczuk

2019

Hum Exp Toxicol

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Tissue-dependent oestrogenic and anti-oestrogenic activity of polycyclic aromatic hydrocarbons (PAHs) has been suggested. In this study, the effect of two PAH mixtures, M1 composed of all 16 priority pollutants and M2 composed of five (noted in the highest levels) compounds, on follicle-stimulating hormone receptor (FSHR) expression, basal or FSH-induced oestradiol (E2) secretion and aromatase cytochrome P450 (P450arom) protein expression, by non-luteinised human granulosa cell line (HGrC1) was determined. In addition, the consequences of gene silencing of oestrogen receptor alfa (siESR1), oestrogen receptor beta (siESR2) and a G protein-coupled receptor (siGPER1) on the above parameters were described. Neither PAH mixture had an effect on basal FSHR protein expression; however, both mixtures increased FSH-induced FSHR expression. Decreased E2 secretion and P450arom expression was also demonstrated. In both basal and FSH treated cells, siESR1 and siGPER1 reversed the inhibitory effect of the mixtures on E2 secretion; however, in siESR2 cells, the inhibitory effect was still observed. This study showed that both classic ESR1 and GPER1 were involved in the inhibitory effect of both PAH mixtures on E2 secretion and confirmed that expression of P450arom could be downregulated through the aryl hydrocarbon receptor and additionally through the ESR2.

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Section: Methodsmentioning

confidence: 99%

Environmental polycyclic aromatic hydrocarbons mixture, in human blood levels, decreased oestradiol secretion by granulosa cells via ESR1 and GPER1 but not ESR2 receptor

Zajda

Gregoraszczuk

2019

Hum Exp Toxicol

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“…Interestingly, we found an inverse proportional increase in CYP1A1 and AhR mRNA levels with EphX1 levels, indicating the role of AhR/CYP1A1 in Pb-induced lung inflammation. It is becoming increasingly clear that the cross-talk between AhR and NF-κB signaling plays an important role in lung toxicity (Ansari et al 2013;Korashy and El-Kadi 2008b;Wang et al 2017;Zajda et al 2017). Importantly, we found that activation of AhR/CYP1A1 in response to Pb was associated with a proportional increase in NF-κB mRNA in the lung tissues of the Pb-exposed group compared with the control.…”

Section: Discussionmentioning

confidence: 57%

“…*p < 0.05 compared to the control (Pb 0 mg/kg b.w.) an important role in lung toxicity (Ansari et al 2013;Korashy and El-Kadi 2008b;Wang et al 2017;Zajda et al 2017). Initially, in this study, we tested the distribution profile of Pb after oral administration to specifically determine which organ is most targeted by Pb.…”

Section: Discussionmentioning

confidence: 99%

Lead Nitrate Induces Inflammation and Apoptosis in Rat Lungs Through the Activation of NF-κB and AhR Signaling Pathways

Attafi

Bakheet

Ahmad

et al. 2022

Environ Sci Pollut Res

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Lead (Pb) is one of the most frequent hazardous air contaminants, where the lungs are particularly vulnerable to its toxicity. However, the Pb distribution and its impact on lung inflammation/apoptosis and particularly the involvement of nuclear factor kappa B (NF-κB) and aryl hydrocarbon receptor (AhR) signaling pathways in Pb-induced lung toxicity have not yet been fully investigated. Adult male Wistar albino rats were exposed to Pb nitrate 25, 50, and 100 mg/kg b.w. orally for 3 days. The histopathological changes of several rat organs were analyzed using hematoxylin and eosin staining. The concentrations of Pb ion in different organ tissues were quantified using inductive coupled plasma mass spectrometry, while gas chromatography-mass spectrometry was used to identify organic compounds. The changes in the mRNA and protein expression levels of inflammatory and apoptotic genes in response to Pb exposure were quantified by using RT-PCR and Western blot analyses, respectively. Treatment of rats with Pb for three consecutive days significantly increased the accumulation of Pb in lung tissues causing severe interstitial inflammation. Pb treatment also increased the percentage of lung apoptotic cells and modulated apoptotic genes (Bc2, p53, and TGF-α), inflammatory markers (IL-4, IL-10, TNF-α), and oxidative stress biomarkers (iNOS, CYP1A1, EphX) in rat lung tissues. These effects were associated with a significant increase in organic compounds, such as 3-nitrotyrosine and myeloperoxidase, and some inorganic elements, such as selenium. Importantly, the Pb-induced lung inflammation and apoptosis were associated with a proportional increase in the expression of NF-κB and AhR mRNAs and proteins. These findings clearly show that Pb induces severe inflammation and apoptosis in rat lungs and suggest that NF-κB and AhR may play a role in Pb-induced lung toxicity.

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“…For example, Zajda and colleagues exposed human non-luteinized granulosa cells to two types of PAC mixtures (M1, mix of the top 16 priority PACs; and M2, top 5 most detected priority PACs in maternal blood) and reported a significant increase in FSH-stimulated FSH receptor expression, and decreased aromatase expression and E2 output ( Zajda et al, 2019 ). However, the authors observed differential expression profiles of AhR and AhR-related targets ( Zajda et al, 2017 ), thus highlighting the difficulty in determining the exact mechanism of toxicity of these complex mixtures.…”

Section: Mechanisms Mediating Pac Ovotoxicitymentioning

confidence: 99%

The effects of polycyclic aromatic compounds (PACs) on mammalian ovarian function

Perono

Petrik

Thomas

et al. 2022

Current Research in Toxicology

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Effects of human blood levels of two PAH mixtures on the AHR signalling activation pathway and CYP1A1 and COMT target genes in granulosa non-tumor and granulosa tumor cell lines

Cited by 36 publications

References 53 publications

Environmental polycyclic aromatic hydrocarbons mixture, in human blood levels, decreased oestradiol secretion by granulosa cells via ESR1 and GPER1 but not ESR2 receptor

Environmental polycyclic aromatic hydrocarbons mixture, in human blood levels, decreased oestradiol secretion by granulosa cells via ESR1 and GPER1 but not ESR2 receptor

Lead Nitrate Induces Inflammation and Apoptosis in Rat Lungs Through the Activation of NF-κB and AhR Signaling Pathways

The effects of polycyclic aromatic compounds (PACs) on mammalian ovarian function

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