Adverse (geno)toxic effects of bisphenol A and its analogues in hepatic 3D cell model

Sendra, Marta; Štampar, Martina; Fras, Katarina; Novoa, Beatriz; Figueras, António; Žegura, Bojana

doi:10.1016/j.envint.2022.107721

Cited by 23 publications

(5 citation statements)

References 119 publications

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“…BPC significantly reduced cell viability in a dose-dependent manner at ≥40 μM ( Figure 2 A). Similar findings for BPAP were reported by Sendra et al [ 20 ], who observed an increase in cell viability of HepG2 spheroids after 24-h exposure to 20 µM BPAP. In the same study BPC at ≥20 μM reduced cell viability after 24-h exposure, but the reduction was not statistically significant.…”

Section: Resultssupporting

confidence: 90%

“…To date, only a few studies have investigated the effects of BPA and its analogues on growth, compactness, and surface area, and these have been conducted on traditional 2D monolayer cultures [ 73 , 74 , 75 ]. The results of the only published study in a 3D HepG2 cell model [ 20 ] show no significant changes in the average surface area after 24 h of exposure to single BPA, BPAP, and BPC compounds compared to the average surface area of the solvent control. In addition, concentrations up to 80 µM of BPs studied did not affect the average surface area of spheroids after prolonged exposure (96 h).…”

Section: Resultsmentioning

confidence: 98%

“…There are almost no publications available in the literature addressing mechanisms of toxicity due to co-exposure to multiple BP analogues or BP analogues together with other environmental toxins. Most of the available toxicity studies have evaluated the effects of a single BP [ 17 , 20 , 44 ]. However, it is extremely important to consider potential additive or synergistic effects caused by a mixture of BPs analogues when studying the mechanisms of action and assessing human health risks.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the increased formation of ROS can lead to the induction of DNA damage. Previously, it was reported that all three bisphenols studied induced increased formation of DNA single-strand breaks in HepG2 spheroids as determined by the comet assay, with BPAP being the most effective [ 20 ]. To fully understand the mechanisms and the potential health risks associated with exposure to these chemicals, further research is needed.…”

Section: Resultsmentioning

confidence: 99%

“…Reports from the late 1990s link BPA to various adverse effects, particularly disruption of the human endocrine system [ 12 , 13 , 14 , 15 ]. In addition, BPA has been shown to have genotoxic properties [ 16 , 17 , 18 , 19 , 20 ], can affect the reproductive, cardiovascular, immunological and respiratory systems, can induce tumours [ 21 , 22 , 23 , 24 , 25 ] and can impair cognitive and behavioural development [ 26 ]. Due to safety concerns, the European Union (EU) has restricted the use of BPA to protect human health and the environment [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Combined Toxic Effects of BPA and Its Two Analogues BPAP and BPC in a 3D HepG2 Cell Model

et al. 2023

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Bisphenol A (BPA) is one of the most commonly used substances in the manufacture of various everyday products. Growing concerns about its hazardous properties, including endocrine disruption and genotoxicity, have led to its gradual replacement by presumably safer analogues in manufacturing plastics. The widespread use of BPA and, more recently, its analogues has increased their residues in the environment. However, our knowledge of their toxicological profiles is limited and their combined effects are unknown. In the present study, we investigated the toxic effects caused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP and BPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed that BPA did not reduce cell viability in HepG2 spheroids after 24-h exposure. In contrast, BPAP and BPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC) decreased cell viability in a dose-dependent manner, but the significant difference was only observed for the combination of BPA/BPC (both at 40 µM). After 96-h exposure, none of the BPs studied affected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cell viability in a dose-dependent manner that was significant for the combination of 4 µM BPA and 4 µM BPAP. None of the BPs and their binary mixtures studied affected the surface area and growth of spheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggered oxidative stress, as measured by the production of reactive oxygen species and malondialdehyde, at both exposure times. Overall, the results suggest that it is important to study the effects of BPs as single compounds. It is even more important to study the effects of combined exposures, as the combined effects may differ from those induced by single compounds.

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Section: Resultssupporting

confidence: 90%