Genotoxic activity of bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF and their mixtures in human hepatocellular carcinoma (HepG2) cells

Hercog, Klara; Maisanaba, Sara; Filipič, Metka; Sollner-Dolenc, Marija; Kač, Lidija; Žegura, Bojana

doi:10.1016/j.scitotenv.2019.05.486

Cited by 120 publications

(78 citation statements)

References 82 publications

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“…BPS and BPAF even had a slight proliferating or more likely cell metabolic activity enhancing effect, which can commonly be observed after exposure to various toxic agents in cell lines as the consequence of increased mitochondrial activity in cell-cycle arrested cells [56]. Our results are in line with previous findings, showing a reduction in cell viability only after exposure to higher concentrations (15 µg/mL) of BPs (BPA, BPS, BPF, and BPAF) in HepG2 cells [46]. Low cytotoxicity was, for these BPs, also reported in other in vitro model systems (human breast adenocarcinoma cells (MCF-7), human 189 cervical epithelial cancer cells (HeLa), mouse fibroblasts (3T3-L1), and rat glioma cells (C6)), with the calculated half-maximal inhibitory concentrations (IC 50 ) generally being in the range of 20-75 µg/mL [57].…”

Section: The Influence Of Cyn Bps and Their Combinations On Cell VIsupporting

confidence: 92%

“…No induction of γH2X was detected in cells exposed to the tested BPs alone except for BPAF, which slightly increased DSB formation. Additionally, in our previous study [46], no induction of DSBs in HepG2 cells at comparable exposure conditions by BPs was observed. BPF and BPAF were found to increase the formation of γH2X at higher concentrations (≥ 10 µg/ml) or at an earlier time point (24 h).…”

Section: Induction Of Dna Double-strand Breaks By Cyn Bps and Theirmentioning

confidence: 64%

“…The influence of single compounds and CYN/BPs combinations on HepG2 cell viability was evaluated with the tetrazolium-based MTS assay. The concentrations of CYN (0.5 µg/ml) and BPs (10 µg/ml) were chosen based on previous findings on the genotoxic effects of CYN [25,27,28] and BPs [46] in HepG2 cells, also considering reported environmental concentrations and the significant daily uptake rate through dietary ingestion in the case of BPA. Although these concentrations are still higher than those reported in the environment and are not expected to be directly relevant for human exposure, they serve the aim of this study, which was to identify the possible DNA damaging effects (induction of DNA DSBs) and potential mechanisms of action of non-cytotoxic concentrations of CYN/BPs binary mixtures.…”

Section: The Influence Of Cyn Bps and Their Combinations On Cell VImentioning

confidence: 99%

“…Similar data for BPA analogues are again scarce. BPF and BPAF were found to induce DNA double-strand breaks in vitro, while BPS was inactive at concentrations up to 20 µg/mL in hepatic cells [46].…”

Section: Introductionmentioning

confidence: 97%

“…Apart from the well-known endocrine disruption effects of BPA, evidence for its potential genotoxicity is accumulating (for a review see: [37,40]). BPA and its metabolites have been reported to induce DNA strand breaks in vitro [44][45][46] and in vivo [47], chromosomal aberrations in vitro [45,48] and in vivo [45,47,48], and to form DNA adducts in vitro [45,49,50] and in vivo [51]. Similar data for BPA analogues are again scarce.…”

Section: Introductionmentioning

confidence: 99%

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Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells

Hercog

Štern

Maisanaba

et al. 2020

Toxins

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Ever-expanding environmental pollution is causing a rise in cyanobacterial blooms and the accumulation of plastics in water bodies. Consequently, exposure to mixtures of cyanotoxins and plastic-related contaminants such as bisphenols (BPs) is of increasing concern. The present study describes genotoxic effects induced by co-exposure to one of the emerging cyanotoxins—cylindrospermopsin (CYN)—(0.5 µg/mL) and BPs (bisphenol A (BPA), S (BPS), and F (BPF); (10 µg/mL)) in HepG2 cells after 24 and 72 h of exposure. The cytotoxicity was evaluated with an MTS assay and genotoxicity was assessed through the measurement of the induction of DNA double strand breaks (DSB) with the γH2AX assay. The deregulation of selected genes (xenobiotic metabolic enzyme genes, DNA damage, and oxidative response genes) was assessed using qPCR. The results showed a moderate reduction of cell viability and induction of DSBs after 72 h of exposure to the CYN/BPs mixtures and CYN alone. None of the BPs alone reduced cell viability or induced DSBs. No significant difference was observed between CYN and CYN/BPs exposed cells, except with CYN/BPA, where the antagonistic activity of BPA against CYN was indicated. The deregulation of some of the tested genes (CYP1A1, CDKN1A, GADD45A, and GCLC) was more pronounced after exposure to the CYN/BPs mixtures compared to single compounds, suggesting additive or synergistic action. The present study confirms the importance of co-exposure studies, as our results show pollutant mixtures to induce effects different from those confirmed for single compounds.

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Section: The Influence Of Cyn Bps and Their Combinations On Cell VIsupporting

confidence: 92%

Section: Induction Of Dna Double-strand Breaks By Cyn Bps and Theirmentioning

confidence: 64%

Section: The Influence Of Cyn Bps and Their Combinations On Cell VImentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells

Hercog

Štern

Maisanaba

et al. 2020

Toxins

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A novel strategy for the study on molecular mechanism of prostate injury induced by 4,4′‐sulfonyldiphenol based on network toxicology analysis

Huang

2023

J of Applied Toxicology

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The study aimed to investigate the underlying molecular mechanisms of prostate injury induced by 4,4′‐sulfonyldiphenol (BPS) exposure and propose a novel research strategy to systematically explore the molecular mechanisms of toxicant‐induced adverse health effects. By utilizing the ChEMBL, STITCH, and GeneCards databases, a total of 208 potential targets associated with BPS exposure and prostate injury were identified. Through screening the potential target network in the STRING database and Cytoscape software, we determined 21 core targets including AKT1, EGFR, and MAPK3. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses conducted through the DAVID database illustrated that the potential targets of BPS in prostatic toxicity were primarily enriched in cancer signaling pathways and calcium signaling pathways. These findings suggest that BPS may actively participate in the occurrence and development of prostate inflammation, prostatic hyperplasia, prostate cancer, and other aspects of prostate injury by regulating prostate cancer cell apoptosis and proliferation, activating inflammatory signaling pathways, and modulating prostate adipocytes and fibroblasts. This research provides a theoretical basis for understanding the molecular mechanism of underlying BPS‐induced prostatic toxicity and establishes a foundation for the prevention and treatment of prostatic diseases associated with exposure to plastic products containing BPS and certain BPS‐overwhelmed environments.

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Genotoxicity of bisphenol AF in rats: Detrimental to male reproductive system and probable stronger micronucleus induction potency than BPA

Zhu,

Cao,

Liu

et al. 2023

J of Applied Toxicology

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Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28‐day multi‐endpoint (Pig‐a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF‐treated groups (0.5, 5, and 50 μg/kg·bw/d), BPA group (10 μg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N‐ethyl‐N‐nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high‐dose recovery group (BPAF‐HR), oil recovery group (oil‐R), ENU recovery group (ENU‐R), and PBS recovery group (PBS‐R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood‐testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.

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Genotoxic activity of bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF and their mixtures in human hepatocellular carcinoma (HepG2) cells

Cited by 120 publications

References 82 publications

Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells

Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells

A novel strategy for the study on molecular mechanism of prostate injury induced by 4,4′‐sulfonyldiphenol based on network toxicology analysis

Genotoxicity of bisphenol AF in rats: Detrimental to male reproductive system and probable stronger micronucleus induction potency than BPA

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