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

BPA analogues Cell proliferation DNA strand breaks Genotoxic In vitro 3D cell model

Journal

Environment international
ISSN: 1873-6750
Titre abrégé: Environ Int
Pays: Netherlands
ID NLM: 7807270

Informations de publication

Date de publication:
01 2023
Historique:
received: 13 10 2022
revised: 05 12 2022
accepted: 23 12 2022
pubmed: 30 12 2022
medline: 24 1 2023
entrez: 29 12 2022
Statut: ppublish

Résumé

Bisphenol A (BPA) is one of the most widely used and versatile chemical compounds in polymer additives and epoxy resins for manufacturing a range of products for human applications. It is known as endocrine disruptor, however, there is growing evidence that it is genotoxic. Because of its adverse effects, the European Union has restricted its use to protect human health and the environment. As a result, the industry has begun developing BPA analogues, but there are not yet sufficient toxicity data to claim that they are safe. We investigated the adverse toxic effects of BPA and its analogues (BPS, BPAP, BPAF, BPFL, and BPC) with emphasis on their cytotoxic and genotoxic activities after short (24-h) and prolonged (96-h) exposure in in vitro hepatic three-dimensional cell model developed from HepG2 cells. The results showed that BPFL and BPC (formed by an additional ring system) were the most cytotoxic analogues that affected cell viability, spheroid surface area and morphology, cell proliferation, and apoptotic cell death. BPA, BPAP, and BPAF induced DNA double-strand break formation (γH2AX assay), whereas BPAF and BPC increased the percentage of p-H3-positive cells, indicating their aneugenic activity. All BPs induced DNA single-strand break formation (comet assay), with BPAP (≥0.1 μM) being the most effective and BPA and BPC the least effective (≥1 μM) under conditions applied. The results indicate that not all of the analogues studied are safer alternatives to BPA and thus more in-depth research is urgently needed to adequately evaluate the risks of BPA analogues and assess their safety for humans.

Identifiants

pubmed: 36580735
pii: S0160-4120(22)00648-1
doi: 10.1016/j.envint.2022.107721
pmc: PMC9875311
pii:
doi:

Substances chimiques

bisphenol A MLT3645I99
Benzhydryl Compounds 0
Phenols 0
DNA 9007-49-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

107721

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Marta Sendra (M)

Department of Biotechnology and Food Science, Faculty of Sciences, University of Burgos, Plaza Misael Bañuelos, 09001 Burgos, Spain; International Research Center in Critical Raw Materials-ICCRAM, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain. Electronic address: msendra@ubu.es.

Martina Štampar (M)

National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, 1000 Ljubljana, Slovenia. Electronic address: martina.stampar@nib.si.

Katarina Fras (K)

National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, 1000 Ljubljana, Slovenia. Electronic address: katarina.fras@nib.si.

Beatriz Novoa (B)

Immunology and Genomics Group, Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Científicas (CSIC), Vigo, Spain. Electronic address: beatriznovoa@iim.csic.es.

Antonio Figueras (A)

Immunology and Genomics Group, Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Científicas (CSIC), Vigo, Spain. Electronic address: antoniofigueras@iim.csic.es.

Bojana Žegura (B)

National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, 1000 Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, 1000 Ljubljana, Slovenia. Electronic address: bojana.zegura@nib.si.

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