Battelle Biomedical Research Center, Columbus, OH 43201, USA.
J Biochem Mol Toxicol. 2011 Jul-Aug;25(4):252-62. doi: 10.1002/jbt.20383. Epub 2011 Mar 9.
Bromine is an industrial chemical that can cause severe cutaneous burns. This study was a preliminary investigation into the effect of cutaneous exposure to bromine vapor using a weanling swine burn model and microarray analysis. Ventral abdominal sites were exposed to a mean calculated bromine vapor concentration of 0.69 g L(-1) for 10 or 20 min. At 48 h postexposure, total RNA from skin samples was isolated, processed, and hybridized to Affymetrix GeneChip Porcine Genome Arrays. Expression analysis revealed that bromine vapor exposure for 10 or 20 min promoted similar transcriptional changes in the number of significantly modulated probe sets. A minimum of 83% of the probe sets was similar for both exposure times. Ingenuity pathways analysis revealed eight common biological functions among the top 10 functions of each experimental group, in which 30 genes were commonly shared among 19 significantly altered signaling pathways. Transcripts encoding heme oxygenase 1, interleukin-1β, interleukin 2 receptor gamma chain, and plasminogen activator inhibitor-1 were identified as common potential therapeutic targets for Phase II/III clinical trial or FDA-approved drugs. The present study is an initial assessment of the transcriptional responses to cutaneous bromine vapor exposure identifying molecular networks and genes that could serve as targets for developing therapeutics for bromine-induced skin injury.
溴是一种工业化学物质,可导致严重的皮肤烧伤。本研究使用新生仔猪烧伤模型和微阵列分析,初步研究了皮肤暴露于溴蒸气的影响。腹部腹侧部位暴露于平均计算的溴蒸气浓度为 0.69 g L(-1),暴露时间为 10 或 20 min。暴露后 48 h,从皮肤样本中分离、处理总 RNA,并与 Affymetrix GeneChip Porcine Genome Arrays 杂交。表达分析表明,暴露于溴蒸气 10 或 20 min 均可促进显著调节的探针集数量的类似转录变化。两种暴露时间的探针集至少有 83%是相似的。Ingenuity 通路分析显示,每个实验组前 10 个功能中有 8 个共同的生物学功能,其中 19 个显著改变的信号通路中有 30 个基因共同共享。编码血红素加氧酶 1、白细胞介素 1β、白细胞介素 2 受体 γ 链和纤溶酶原激活物抑制剂 1 的转录本被鉴定为二期/三期临床试验或 FDA 批准药物的共同潜在治疗靶点。本研究初步评估了皮肤暴露于溴蒸气后的转录反应,确定了可作为开发治疗溴诱导皮肤损伤的治疗靶点的分子网络和基因。