Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
Sci Total Environ. 2011 May 1;409(11):2040-8. doi: 10.1016/j.scitotenv.2011.01.055. Epub 2011 Mar 21.
This study investigated the effects of two mixtures of persistent organic pollutants (POPs) on steroidogenesis in the H295R cell line. The two mixtures were obtained from the livers of burbot (Lota lota) caught in two Norwegian lakes (Mjøsa and Losna) with different contaminant profiles. Steroid hormone levels in the cell culture medium and mRNA levels of 16 genes involved in steroidogenesis were investigated. The crude Lake Mjøsa extract had to be diluted ten times more than the Lake Losna extract in order to prevent cytotoxicity. The ten times diluted Lake Mjøsa mixture had higher levels of DDT and derivates (∑DDTs, 1.7 times) and brominated flame retardants (∑BDEs and HBCD, 15-25 times) than the Lake Losna mixture, which, on the other hand, had higher concentrations of ∑PCBs (1.5 times higher) and also of HCB, ∑HCH isomers and ∑chlordane isomers (5-20 times higher). In the cell culture media, only cortisol levels were increased at the highest exposure concentration to the Lake Mjøsa mixture, while both cortisol and estradiol levels were increased following exposure to the two highest Lake Losna mixture exposure concentrations. Testosterone levels decreased only at the highest exposure concentration of the Lake Losna mixture. Multivariate models suggested that ∑PCBs, and to a lesser extent ∑DDTs, were responsible for the cortisol responses, while estradiol and testosterone alterations were best explained by HCB and ∑PCBs, respectively. Exposure to the mixtures generally increased mRNA levels, with smaller effects exerted by the Lake Mjøsa mixture than the Lake Losna mixture. It was concluded that both mixtures affected steroidogenesis in the H295R cells. Small differences in mixture composition, rather than the high content of brominated flame retardants in the Lake Mjøsa mixture, were suggested to be the most probable reason for the apparent differences in potencies of the two mixtures.
本研究调查了两种持久性有机污染物(POPs)混合物对 H295R 细胞系类固醇生成的影响。这两种混合物是从在两个具有不同污染物特征的挪威湖泊(Mjøsa 和 Losna)捕获的欧白鲑(Lota lota)肝脏中获得的。研究了细胞培养物中类固醇激素水平和参与类固醇生成的 16 个基因的 mRNA 水平。为了防止细胞毒性,必须将 Lake Mjøsa 粗提取物稀释十倍以上,而 Lake Losna 提取物则要稀释十倍。十倍稀释的 Lake Mjøsa 混合物中滴滴涕及其衍生物(∑DDTs,高 1.7 倍)和溴化阻燃剂(∑BDEs 和 HBCD,高 15-25 倍)的水平高于 Lake Losna 混合物,而后者的 ∑PCBs(高 1.5 倍)浓度以及 HCB、∑HCH 异构体和∑氯丹异构体(高 5-20 倍)浓度较高。在细胞培养物培养基中,只有在暴露于 Lake Mjøsa 混合物的最高浓度时,皮质醇水平才会升高,而在暴露于 Lake Losna 混合物的两个最高浓度时,皮质醇和雌二醇水平均升高。只有在暴露于 Lake Losna 混合物的最高浓度时,睾丸激素水平才会降低。多变量模型表明,∑PCBs 以及在较小程度上,∑DDTs 负责皮质醇反应,而雌二醇和睾丸激素的改变分别由 HCB 和∑PCBs 最佳解释。混合物的暴露通常会增加 mRNA 水平,而 Lake Mjøsa 混合物的影响小于 Lake Losna 混合物。研究得出的结论是,两种混合物均影响 H295R 细胞中的类固醇生成。混合物组成的微小差异,而不是 Lake Mjøsa 混合物中高溴化阻燃剂含量,被认为是两种混合物效力明显差异的最可能原因。