关键词: DNA base damage HepG2 apoptosis bisphenols genotoxicity immunotoxicity

来  源:   DOI:10.1093/toxres/tfae127   PDF(Pubmed)

Abstract:
UNASSIGNED: Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and \"low dose toxicity\". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased.
UNASSIGNED: In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2\'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects.
UNASSIGNED: Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.
摘要:
双酚广泛用于聚碳酸酯塑料和树脂涂料的生产。双酚A(BPA)被认为会引起广泛的不良影响和“低剂量毒性”。随着寻找BPA的替代物质,其他双酚衍生物,即双酚F(BPF)和双酚S(BPS)的使用已经增加。
在当前的研究中,我们旨在评估双酚衍生物对免疫和凋亡标志物以及HepG2细胞DNA损伤的计算机预测抑制浓度50(pIC50)。此外,凋亡,BPA的遗传毒性和免疫毒性作用,比较测定了BPF和BPS。通过检测不同的caspase活性来评估双酚对细胞凋亡的影响。通过测量8-羟基-2'-脱氧鸟苷(8-OHdG)和8-氧鸟嘌呤糖基化酶(OGG1)的水平来评估双酚的遗传毒性作用。为了确定双酚衍生物的免疫毒性作用,白细胞介素4(IL-4)和白细胞介素10(IL-10)的水平,转化生长因子-β(TGF-β)和肿瘤坏死因子-α(TNF-α),已知由HepG2细胞表达,被测量。结果:计算机数据表明,低剂量下所有双酚都可能导致免疫和凋亡标志物的改变以及DNA损伤。体外数据显示,所有双酚衍生物在抑制浓度30s(IC30s)下都能影响免疫标记。此外,BPF和BPS也可能具有凋亡免疫毒性作用。
需要进一步进行计算机和体内研究,以检查替代双酚衍生物的毒性作用。
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