Adverse (geno)toxic effects of bisphenol A and its analogues in hepatic 3D cell model
Creators
- 1. 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.
- 2. National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, 1000 Ljubljana, Slovenia.
- 3. Immunology and Genomics Group, Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Científicas (CSIC), Vigo, Spain.
- 4. National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, 1000 Ljubljana, Slovenia
Description
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.
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