Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line
Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line
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DOI：
10.1016/j.tox.2008.09.024
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发表时间：
2009-01-08
期刊：
影响因子：
4.5
通讯作者：
Chagnon, Marie-Christine
中科院分区：
文献类型：
--
作者：
Cabaton, Nicolas;Dumont, Coralie;Chagnon, Marie-Christine
作为环境和食品污染物，人类可接触到双(羟基苯基)甲烷(双酚F或BPF)及其衍生物。本研究旨在利用体外方法鉴定和比较BPF、BFDGE和两种BPF代谢物的毒性。当根据OECD指南进行Ames检测时，BPF没有在细菌中诱导任何基因突变。相反，利用人细胞株和彗星试验，我们证明了BPF和双酚F二缩水甘油醚(BFDGE)在非细胞毒性浓度下对HepG2细胞DNA片段有明显的抑制作用。DHB也是阳性的，但在更高的浓度下，接近其溶解极限。BPF和DHB在微核试验中均未引起阳性反应。BFDGE对细胞微核率的增加主要是由于细胞毒作用。在内分泌活性方面，BPF以浓度依赖的方式瞬时增强了HepG2细胞的荧光素酶活性，DHB也引起了阳性反应，但在最高浓度下。不同雌激素受体(ER)参与的HepG2细胞的雌激素反应不同。在稳定表达pMMTV-neo-Luc的MDA-kb(2)细胞系中，只有BPF在最高浓度(10(-5)M)时具有抗雄激素作用。然后，我们利用人类细胞株，特别是HepG2细胞，证明了BPF在遗传毒性和内分泌活性方面是最有毒的化合物，而BPF-OH是大鼠给药时在尿中发现的游离代谢物DHB和BPF-OH。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Human can be exposed to bis(hydroxyphenyl)methane (bisphenol F or BPF) and its derivatives as environment and food's contaminants. This study was investigated to identify and to compare toxic potency of BPF, BFDGE, and two of BPF metabolites using in vitro methods. BPF did not induce any genic mutation in bacteria when the Ames test was performed according to the OECD guideline. In contrast, using Human cell lines and Comet assay, we demonstrated that BPF and Bisphenol F Diglycidyl Ether (BFDGE) were effective on HepG2 cell DNA fragmentation at non-cytotoxic concentrations. DHB was also positive but at higher concentrations, near its limit of solubility. Neither BPF, nor DHB induced a positive response in the micronucleus assay. The increase of micronuclei observed when cells were exposed to BFDGE was mostly due to a cytotoxic effect. Concerning endocrine activities, BPF increased the luciferase activity in HepG2 cells transiently transfected with a concentration dependant pattern, DHB also induced a positive response but at highest concentrations. Estrogenic responses in the HepG2 cells differed with the estrogen receptor (ER) involved. Using MDA-kb(2) cell line stably transfected with pMMTV-neo-Luc, only BPF was anti-androgenic at the highest concentration (10(-5) M). Then, we demonstrated using human cell lines, especially HepG2, BPF was the most toxic compound in term of genotoxicity and endocrine activities compared to DHB and BPF-OH, the free metabolites identified in rat urine when BPF was administrated to rats. (C) 2008 Elsevier Ireland Ltd. All rights reserved.