Ku Hyun-Ok, Jeong Sang-Hee, Kang Hwan-Goo, Pyo Hyun-Mi, Cho Joon-Hyoung, Son Seong-Wan, Ryu Doug-Young
Toxicology and Chemistry Division, National Veterinary Research and Quarantine Service, Anyang, Republic of Korea.
Toxicol Lett. 2008 Feb 28;177(1):1-9. doi: 10.1016/j.toxlet.2007.12.003. Epub 2008 Feb 1.
There has been some concern that certain non-sensitizing irritants may yield false positive results in the murine local lymph node assay (LLNA). This study compared gene expression profiles in lymph nodes draining skin following exposure to sensitizers and irritants, to identify gene transcripts that could distinguish sensitizers from irritants. After treating CBA/N mouse ears for 3 days with the sensitizers 1-chloro-2,4-dinitrobenzene, 2-phenyl-4-ethoxymethylene-5-oxazolone, or toluene-2,4-diisocyanate or the non-sensitizing irritants croton oil or nonanoic acid, auricular lymph nodes and ear tissues were excised. Sensitizer-induced changes in parameters such as ear thickness, lymph node weight, and cell count also occurred in irritant-treated mouse tissues. However, gene transcripts such as Ifi27, Il12rb1, Ifng, and Zbp1, which are related to T-cell activation, were shown by gene expression microarrays and real-time RT-PCR analyses to be up-regulated in auricular lymph nodes by sensitizers exclusively. These findings suggest that gene expression analysis may enable distinction between sensitizing chemicals and non-sensitizing irritants.
有人担心某些非致敏性刺激物可能会在小鼠局部淋巴结试验（LLNA）中产生假阳性结果。本研究比较了暴露于致敏剂和刺激物后引流皮肤的淋巴结中的基因表达谱，以确定能够区分致敏剂和刺激物的基因转录本。在用致敏剂1-氯-2,4-二硝基苯、2-苯基-4-乙氧基亚甲基-5-恶唑酮或甲苯-2,4-二异氰酸酯或非致敏性刺激物巴豆油或壬酸处理CBA/N小鼠耳朵3天后，切除耳淋巴结和耳组织。致敏剂引起的诸如耳厚度、淋巴结重量和细胞计数等参数的变化也发生在经刺激物处理的小鼠组织中。然而，通过基因表达微阵列和实时RT-PCR分析表明，与T细胞活化相关的基因转录本，如Ifi27、Il12rb1、Ifng和Zbp1，仅在致敏剂处理的耳淋巴结中上调。这些发现表明基因表达分析可能有助于区分致敏化学物质和非致敏性刺激物。
