Tani Hidenori, Takeshita Jun-Ichi, Aoki Hiroshi, Nakamura Kaoru, Abe Ryosuke, Toyoda Akinobu, Endo Yasunori, Miyamoto Sadaaki, Gamo Masashi, Sato Hiroaki, Torimura Masaki
Environmental Management Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Onogawa, Tsukuba, Ibaraki, Japan.
Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST), Onogawa, Tsukuba, Ibaraki, Japan.
PLoS One. 2017 Jul 27;12(7):e0182032. doi: 10.1371/journal.pone.0182032. eCollection 2017.
Although it is not yet possible to replace in vivo animal testing completely, the need for a more efficient method for toxicity testing, such as an in vitro cell-based assay, has been widely acknowledged. Previous studies have focused on mRNAs as biomarkers; however, recent studies have revealed that non-coding RNAs (ncRNAs) are also efficient novel biomarkers for toxicity testing. Here, we used deep sequencing analysis (RNA-seq) to identify novel RNA biomarkers, including ncRNAs, that exhibited a substantial response to general chemical toxicity from nine chemicals, and to benzene toxicity specifically. The nine chemicals are listed in the Japan Pollutant Release and Transfer Register as class I designated chemical substances. We used undifferentiated mouse embryonic stem cells (mESCs) as a simplified cell-based toxicity assay. RNA-seq revealed that many mRNAs and ncRNAs responded substantially to the chemical compounds in mESCs. This finding indicates that ncRNAs can be used as novel RNA biomarkers for chemical safety screening.
虽然目前还不可能完全取代体内动物试验，但人们已经广泛认识到需要一种更有效的毒性测试方法，如基于体外细胞的检测方法。以往的研究主要集中在将mRNA作为生物标志物；然而，最近的研究表明，非编码RNA（ncRNA）也是毒性测试中有效的新型生物标志物。在这里，我们使用深度测序分析（RNA测序）来鉴定新型RNA生物标志物，包括ncRNA，它们对九种化学物质的一般化学毒性以及对苯毒性有显著反应。这九种化学物质在日本污染物排放和转移登记册中被列为一类指定化学物质。我们使用未分化的小鼠胚胎干细胞（mESC）作为简化的基于细胞的毒性检测方法。RNA测序显示，许多mRNA和ncRNA对mESC中的化合物有显著反应。这一发现表明，ncRNA可作为化学安全筛查的新型RNA生物标志物。
