Wu Minghong, Pan Chenyuan, Chen Zhong, Jiang Lihui, Lei Penghui, Yang Ming
School of Environmental and Chemical Engineering, Shanghai University, P.O. Box 144, Shangda Road 99, Shanghai, 200444, China.
Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Environ Sci Pollut Res Int. 2017 Mar;24(7):6611-6621. doi: 10.1007/s11356-016-8351-0. Epub 2017 Jan 12.
Bisphenol A (BPA) is a well-known endocrine-disrupting chemical that is ubiquitously present in the environment. In the present study, 4-h post-fertilization (hpf) zebrafish embryos were exposed to various environmentally relevant concentrations of BPA (0.1, 1, 10, 100, and 1000 μg/L) until 72 and 168 hpf, and the accumulation pattern of BPA and its potential to induce toxicity through apoptosis were determined. Compared to BPA concentrations in larvae at 168 hpf, BPA concentrations in embryos exposed until 72 hpf were at relatively higher levels (p < 0.05) with higher bioconcentration factor (BCF) values. The nonlinear fitting analysis indicated that the BCF values of BPA in fish embryos/larvae were significantly correlated to the log10-transformed BPA exposure concentrations in water in an inverse concentration-dependent manner. Fish accumulated more BPA as the exposure concentrations increased; however, their accumulation capacity of BPA declined and tended to be saturated in the high exposure groups of BPA. Moreover, caspase-3 activity was significantly induced upon BPA exposure at 0.1, 1, 10, and 100 μg/L BPA at 72 hpf, and also at 10 and 100 μg/L BPA at 168 hpf. Correspondingly, exposure to 10 and 100 μg/L of BPA significantly increased the DNA fragmentation in the extracted DNA at 168 hpf as determined by DNA ladder analysis. In addition, the expression patterns of four genes related to apoptosis including caspase-3, bax, p53, and c-jun were significantly up-regulated (p < 0.05) in fish embryos/larvae upon BPA exposure at 72 and 168 hpf. Our results revealed that low and environmentally relevant concentrations of BPA could be significantly accumulated in zebrafish and induced apoptosis with involvement of the regulation of caspase-3 and other apoptosis-related genes.
双酚A(BPA)是一种广为人知的内分泌干扰化学物质,在环境中普遍存在。在本研究中,将受精后4小时(hpf)的斑马鱼胚胎暴露于各种与环境相关浓度的双酚A(0.1、1、10、100和1000μg/L),直至72和168 hpf,并测定双酚A的积累模式及其通过凋亡诱导毒性的潜力。与168 hpf时幼虫体内的双酚A浓度相比,暴露至72 hpf的胚胎体内双酚A浓度处于相对较高水平(p<0.05),生物富集因子(BCF)值更高。非线性拟合分析表明,双酚A在鱼类胚胎/幼虫中的BCF值与水中经log10转换的双酚A暴露浓度呈显著负浓度依赖性相关。随着暴露浓度的增加,鱼类积累的双酚A更多;然而,它们对双酚A的积累能力下降,并在双酚A高暴露组中趋于饱和。此外,在72 hpf时,暴露于0.1、1、10和100μg/L双酚A时,caspase-3活性显著诱导,在168 hpf时,暴露于10和100μg/L双酚A时也显著诱导。相应地,通过DNA梯状分析确定,在168 hpf时,暴露于10和100μg/L双酚A显著增加了提取DNA中的DNA片段化。此外,在72和168 hpf时,暴露于双酚A的鱼类胚胎/幼虫中,包括caspase-3、bax、p53和c-jun在内的四个与凋亡相关基因的表达模式显著上调(p<0.05)。我们的结果表明,低浓度且与环境相关的双酚A可在斑马鱼中显著积累,并通过caspase-3和其他凋亡相关基因的调控诱导凋亡。