DNA Microarray Data Analysis

作为NTPs努力表征多溴联苯醚（PBDE）毒性的一部分，我以前帮助评估转录反应PBDE混合物（DE-71）在雄性和雌性大鼠幼仔和雄性大鼠的肝脏样本，在一项研究中，DE-71诱导的肝脏基因转录变化与脂质和代谢途径。随后，我们研究了出生后第4天和出生后第22天子宫内暴露/出生后暴露后DE-71及其同系物2，2，4，4-四溴二苯醚（BDE-47）的转录组学变化。我们还比较了三个传统的和六个新兴的溴化阻燃剂在雄性Sprague-Dawley大鼠暴露五天后的影响。一份单独的出版物描述了生成的大型毒理基因组学数据集，以统计学方式比较9种阻燃化学品的多个剂量组的对照反应，并对每种化学品进行基因组基准剂量计算。暴露于多溴二苯醚-47后，Nrf 2抗氧化途径的转录本上调幅度最大，但暴露于十溴二苯醚、六溴环十二烷、三丁基溴化铵和六溴代一氧化碳后，该途径也上调。本研究的数据已保存在单独的出版物中。我正在合作综合从这些出版物中获得的信息，以发现在多溴联苯醚暴露后持续激活的途径和基因。该项目正在进行中。 在另一个项目中，我们通过吸入将B6 C3 F1/N小鼠暴露于钴金属粉尘（CMD）以研究啮齿动物肺泡/细支气管癌（ABC）。在错误发现率阈值为0.05时，与对照组相比，自发ABC中共有11，557个转录本发生变化，与对照组相比，CMD暴露ABC中共有12，420个转录本发生变化。自发和CMD暴露变化之间共有8，520个转录本变化。自发形成或由于CMD暴露的ABC的转录组学分析包含与MAPK信号传导和氧化应激相关的变化。 编码Nox 4和Ereg的基因在CMD暴露的小鼠中上调。这里的数据表明，氧化应激在CMD诱导的啮齿类动物肺癌发生中起着重要作用，这也可能与人类有关。

As part of NTPs efforts to characterize polybrominated diphenyl ether (PBDE) toxicity, I previously helped to evaluate the transcriptional response to a PBDE mixture (DE-71) in liver samples of male and female rat pups, and male rats, in a study that associated DE-71-induced liver gene-transcript changes with lipid and metabolic pathways. We later investigated the transcriptomic changes in response to DE-71 and its congener, 2,2,4,4-tetra-bromodiphenyl ether (BDE-47), on postnatal day 4 and postnatal day 22 after in utero exposure/postnatal day exposure. We also compared the effects of three legacy and six emerging brominated flame retardants in male Sprague-Dawley rats following five-day exposure. A separate publication describes the large toxicogenomics data set generated to statistically compare control responses to those from multiple dose groups across the nine flame retardant chemicals and perform genomic benchmark dose calculations for each chemical. Transcripts underlying the Nrf2 antioxidant pathway were upregulated to the greatest extent after exposure to PBDE-47, but this pathway was also upregulated after decaBDE, HBCD, TBB and HCBCO exposure. The data for this study has been deposited in a separate publication. I am collaborating to synthesize the information obtained from these publications to discover the pathways and genes that are consistently activated in response to PBDE exposure. This project is ongoing. In another project, we exposed B6C3F1/N mice to cobalt metal dust (CMD) by inhalation to investigate rodent alveolar/bronchiolar carcinomas (ABCs). At a false discovery rate threshold of 0.05, a total of 11,557 transcripts were changed in spontaneous ABCs compared to controls, and 12,420 transcripts were changed in CMD exposed ABCs compared to controls.8,520 transcript changes were shared between spontaneous and CMD exposed changes. Transcriptomic analysis of ABCs that formed spontaneously or due to CMD exposure contained changes related to MAPK signaling and oxidative stress. The genes encoding Nox4 and Ereg was upregulated in CMD-exposed mice. The data here suggest that oxidative stress plays a significant role in CMD-induced pulmonary carcinogenesis in rodents, which may also be relevant in humans.