Non-coplanar and coplanar polychlorinated biphenyls potentiate genotoxicity of aflatoxin B1 in a human hepatocyte line by enhancing CYP1A2 and CYP3A4 expression

Chen, Yuting; Liu, Yungang

doi:10.1016/j.envpol.2018.12.041

Cited by 41 publications

(14 citation statements)

References 39 publications

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“…The obtained AFB1 IC 50 values were within the range of IC 50 (1-16.9 µM) measured in previous studies made in HepG2 cells (a human hepatoma cell line) [61,62]. Interestingly, we also noticed that AFB1 cytotoxicity largely increased (lower IC 50 ) when cells were pre-treated with PCB126, as recently demonstrated in human hepatocytes [63], thus suggesting the presence of additive/synergistic effects, possibly mediated via AHR receptors. Nevertheless, while PCB126 is a well-known AHR-ligand/agonist [60], this is not yet proven for AFB1 and, to a wider extent, aflatoxins [64].…”

Section: Aflatoxin B1 Cytotoxicitysupporting

confidence: 88%

“…Assuming the metabolic competence of fetal hepatocytes is lower compared to that of adult liver cells, we opted for pre-treatment with an AHR agonist, i.e., PCB126, to increase the cell line metabolic competence, hence the responsiveness to AFB1. Nonetheless, the combined use of PCB126 and AFB1 is not novel [63,67]. No information on the BFH12 transcriptomic changes resulting from exposure to PCB126 was available in the literature; hence, a first set of preliminary experiments was undertaken to define the best PCB126 incubation protocol to boost the cellular whole-transcriptomic response to AFB1.…”

Section: Preliminary Evaluations Of Bfh12 Responsiveness To Pcb126mentioning

confidence: 99%

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Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Pauletto

Tolosi²,

Giantin³

et al. 2020

Toxins

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Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, exposure to AFB1-contaminated feed may cause several untoward effects, liver damage being one of the most devastating ones. In the present study, we assessed in vitro the transcriptional changes caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). To boost the cellular response to AFB1, cells were pre-treated with the co-planar PCB 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), a known aryl hydrocarbon receptor agonist. Three experimental groups were considered: cells exposed to the vehicle only, to PCB126, and to PCB126 and AFB1. A total of nine RNA-seq libraries (three replicates/group) were constructed and sequenced. The differential expression analysis showed that PCB126 induced only small transcriptional changes. On the contrary, AFB1 deeply affected the cell transcriptome, the majority of significant genes being associated with cancer, cellular damage and apoptosis, inflammation, bioactivation, and detoxification pathways. Investigating mRNA perturbations induced by AFB1 in cattle BFH12 cells will help us to better understand AFB1 toxicodynamics in this susceptible and economically important food-producing species.

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Section: Aflatoxin B1 Cytotoxicitysupporting

confidence: 88%

Section: Preliminary Evaluations Of Bfh12 Responsiveness To Pcb126mentioning

confidence: 99%

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Pauletto

Tolosi²,

Giantin³

et al. 2020

Toxins

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“…TCDD and co-planar PCBs can bind to the aryl hydrocarbon receptor (AHR) (Barouki et al, 2012, Bock, 2019, Van den Berg et al, 1998 while non-coplanar PCBs cannot bind to AHR although they can interact with its signaling mechanisms. They may as well activate the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) (Chen and Liu, 2019). Dioxins and PCBs can also interact with the estrogen and thyroid signaling pathways, respectively (Diamanti-Kandarakis et al, 2009, Casals-Casas and Desvergne, 2011, Pavek, 2016.…”

Section: Introductionmentioning

confidence: 99%

Exposure to pollutants altered glucocorticoid signaling and clock gene expression in female mice. Evidence of tissue- and sex-specificity

et al. 2021

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“…Apart from the above-mentioned contaminants, AFs can interact with many other toxic substances from the environment. For example, polychlorinated biphenyls (PCB) may potentiate/enhance the genotoxicity effect of AFB 1 in the human hepatocyte line (L-02 cell line) by enhancing CYP1A1, CYP1A2, and CYP3A4 expression [141].…”

Section: Toxicological Interactions Of Aflatoxins With Other Contaminantsmentioning

confidence: 99%

Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation

Pickova

Ostrý

Toman

et al. 2021

Toxins

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In the early 1960s the discovery of aflatoxins began when a total of 100,000 turkey poults died by hitherto unknown turkey “X” disease in England. The disease was associated with Brazilian groundnut meal affected by Aspergillus flavus. The toxin was named Aspergillus flavus toxin—aflatoxin. From the point of view of agriculture, aflatoxins show the utmost importance. Until now, a total of 20 aflatoxins have been described, with B1, B2, G1, and G2 aflatoxins being the most significant. Contamination by aflatoxins is a global health problem. Aflatoxins pose acutely toxic, teratogenic, immunosuppressive, carcinogenic, and teratogenic effects. Besides food insecurity and human health, aflatoxins affect humanity at different levels, such as social, economical, and political. Great emphasis is placed on aflatoxin mitigation using biocontrol methods. Thus, this review is focused on aflatoxins in terms of historical development, the principal milestones of aflatoxin research, and recent data on their toxicity and different ways of mitigation.

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Non-coplanar and coplanar polychlorinated biphenyls potentiate genotoxicity of aflatoxin B1 in a human hepatocyte line by enhancing CYP1A2 and CYP3A4 expression

Cited by 41 publications

References 39 publications

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Exposure to pollutants altered glucocorticoid signaling and clock gene expression in female mice. Evidence of tissue- and sex-specificity

Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation

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