DNA Microarray Data Analysis

本实验探讨了出生后22日龄Wistar汉族大鼠暴露于五溴二苯醚(PBDE)对仔鼠的影响。多溴联苯醚-47是多溴二苯醚混合物(DE-71)的同系物，被选为测试多溴二苯醚的同系物，以比较多溴二苯醚-47的毒性和DE-71的毒性。在宫内和出生后分别以0、0.1、15和50 mg/kg的化学浓度灌胃进行暴露。暴露于PBDE-47和DE-71均导致小叶中心肥大和肝脏脂肪改变，并在PND 22降低血清甲状腺激素水平。肝脏转录改变包括诱导细胞色素P450转录本水平和上调Nrf2抗氧化途径转录本和上调ABC膜转运蛋白。这些转录变化表明，长期接触PBDE-47和DE-71可能是一种肝脏毒素或致癌物质。基因组基准剂量浓度计算表明，PBDE-47暴露导致比DE-71暴露更低的基准剂量浓度。

We explored the effect of pentabromodiphenyl ether (PBDE) exposure on Wistar Han rats pups on postnatal day 22. PBDE-47 is a congener of a PBDE mixture (DE-71) that was chosen as the test PBDE congener to compare PBDE-47 toxicity to the toxicity of DE-71. In utero and postnatal exposure was performed using chemical concentrations of 0, 0.1, 15, and 50 mg/kg by gavage. Both PBDE-47 and DE-71 exposure led to centrilobular hypertrophy and fatty change in liver and reduced serum thyroxin levels by PND 22. Liver transcriptomic changes included induced cytochrome p450 transcript levels and up-regulation of Nrf2 antioxidant pathway transcripts and up-regulation of ABC membrane transport transcripts. These transcriptional changes suggest that exposure to PBDE-47 and DE-71 could be a liver toxin or carcinogen after long-term exposure. A genomic benchmark dose concentration calculation showed that PBDE-47 exposure led to lower benchmark dose concentration than exposure to DE-71.