Division of Inhalation Toxicology, KIT Jeongeup Campus, 1051, Shinjeong-dong, Jeongeup, Jeollabuk-do, Korea.
Arch Toxicol. 2010 Mar;84(3):191-203. doi: 10.1007/s00204-009-0486-z.
Many in the welding industry suffer from bronchitis, lung function changes, metal fume fever, and diseases related to respiratory damage. These phenomena are associated with welding fumes; however, the mechanism behind these findings remains to be elucidated. In this study, the lungs of cynomolgus monkeys were exposed to MMA-SS welding fumes for 229 days and allowed to recover for 153 days. After the exposure and recovery period, gene expression profiles were investigated using the Affymetrix GeneChip Human U133 plus 2.0. In total, it was confirmed that 1,116 genes were up-or downregulated (over 2-fold changes, P\0.01) for the T1 (31.4 ± 2.8 mg/m3) and T2 (62.5 ± 2.7 mg/m3) dose groups. Differentially expressed genes in the exposure and recovery groups were analyzed, based on hierarchical clustering, and were imported into Ingenuity Pathways Analysis to analyze the biological and toxicological functions. Functional analysis identified genes involved in immunological disease in both groups. Additionally, differentially expressed genes in common between monkeys and rats following welding fume exposure were compared using microarray data, and the gene expression of selected genes was verified by real-time PCR. Genes such as CHI3L1, RARRES1, and CTSB were up-regulated and genes such as CYP26B1, ID4, and NRGN were down-regulated in both monkeys and rats following welding fume exposure. This is the first comprehensive gene expression profiling conducted for welding fume exposure in monkeys, and these expressed genes are expected to be useful in helping to understand transcriptional changes in monkey lungs after welding fume exposure.
许多焊接行业从业者患有支气管炎、肺功能改变、金属烟热和与呼吸道损伤相关的疾病。这些现象与焊接烟尘有关；然而，这些发现的背后机制仍有待阐明。在这项研究中，食蟹猴的肺部暴露于 MMA-SS 焊接烟尘中 229 天，并允许其恢复 153 天。暴露和恢复期结束后，使用 Affymetrix GeneChip Human U133 plus 2.0 研究基因表达谱。总共证实了 T1（31.4±2.8mg/m3）和 T2（62.5±2.7mg/m3）剂量组的 1116 个基因表达上调或下调（超过 2 倍变化，P\0.01）。基于层次聚类分析，对暴露组和恢复组的差异表达基因进行了分析，并将其导入 Ingenuity Pathways Analysis 以分析生物学和毒理学功能。功能分析鉴定了两组中与免疫性疾病相关的基因。此外，使用微阵列数据比较了猴子和大鼠在暴露于焊接烟尘后共同差异表达的基因，并通过实时 PCR 验证了选定基因的表达。暴露于焊接烟尘后，猴子和大鼠中的 CHI3L1、RARRES1 和 CTSB 等基因上调，CYP26B1、ID4 和 NRGN 等基因下调。这是首次在猴子中进行的焊接烟尘暴露的综合基因表达谱分析，这些表达的基因有望有助于理解猴子肺部暴露于焊接烟尘后的转录变化。
