Yadetie Fekadu, Karlsen Odd André, Eide Marta, Hogstrand Christer, Goksøyr Anders
Department of Molecular Biology, University of Bergen, Bergen, Norway.
BMC Genomics. 2014 Jun 17;15(1):481. doi: 10.1186/1471-2164-15-481.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with harmful effects in animals and humans. Although PCB 153 is one of the most abundant among PCBs detected in animal tissues, its mechanism of toxicity is not well understood. Only few studies have been conducted to explore genes and pathways affected by PCB 153 by using high throughput transcriptomics approaches. To obtain better insights into toxicity mechanisms, we treated juvenile Atlantic cod (Gadus morhua) with PCB 153 (0.5, 2 and 8 mg/kg body weight) for 2 weeks and performed gene expression analysis in the liver using oligonucleotide arrays.
Whole-genome gene expression analysis detected about 160 differentially regulated genes. Functional enrichment, interactome, network and gene set enrichment analysis of the differentially regulated genes suggested that pathways associated with cell cycle, lipid metabolism, immune response, apoptosis and stress response were among the top significantly enriched. Particularly, genes coding for proteins in DNA replication/cell cycle pathways and enzymes of lipid biosynthesis were up-regulated suggesting increased cell proliferation and lipogenesis, respectively.
PCB 153 appears to activate cell proliferation and lipogenic genes in cod liver. Transcriptional up-regulation of marker genes for lipid biosynthesis resembles lipogenic effects previously reported for persistent organic pollutants (POPs) and other environmental chemicals. Our results provide new insights into mechanisms of PCB 153 induced toxicity.
多氯联苯（PCBs）是持久性有机污染物（POPs），对动物和人类具有有害影响。尽管PCB 153是在动物组织中检测到的多氯联苯中含量最高的一种，但其毒性机制尚未完全了解。只有少数研究使用高通量转录组学方法探索受PCB 153影响的基因和途径。为了更好地了解毒性机制，我们用PCB 153（0.5、2和8毫克/千克体重）处理幼年大西洋鳕鱼（Gadus morhua）2周，并使用寡核苷酸阵列对肝脏进行基因表达分析。
全基因组基因表达分析检测到约160个差异调节基因。对差异调节基因的功能富集、相互作用组、网络和基因集富集分析表明，与细胞周期、脂质代谢、免疫反应、细胞凋亡和应激反应相关的途径在最显著富集的途径中。特别是，DNA复制/细胞周期途径中的蛋白质编码基因和脂质生物合成酶上调，分别表明细胞增殖和脂肪生成增加。
PCB 153似乎激活了鳕鱼肝脏中的细胞增殖和脂肪生成基因。脂质生物合成标记基因的转录上调类似于先前报道的持久性有机污染物（POPs）和其他环境化学物质的脂肪生成作用。我们的结果为PCB 153诱导毒性的机制提供了新的见解。
