Department of Pharmacology and Toxicology, University of Navarra, 31008 Pamplona, Spain.
Food Chem Toxicol. 2013 Sep;59:766-83. doi: 10.1016/j.fct.2013.05.043. Epub 2013 Jun 6.
The mycotoxin Ochratoxin A (OTA) is a potent renal carcinogen in male rats. Transcriptomic studies on OTA (4 in vitro, 6 in vivo, 2 in vitro/in vivo) have been reviewed. The aim of 6 of them was mainly mechanistic whereas the rest had mostly predictive (1) or evaluation (5) purposes. An overall tendency towards gene expression downregulation was observed, probably as a result of protein synthesis inhibition. DNA damage response genes were not deregulated in most of the studies. Genes involved in acute renal injury, cell survival and cell proliferation were upregulated in several in vivo studies. Apoptosis genes were deregulated in vitro but less affected in vivo; activation of several MAPKs has been observed. Many genes related to oxidative stress or involved in cell-to-cell interaction pathways (Wnt) or cytoskeleton structure appeared to be deregulated either in vitro or in vivo. Regucalcin was highly downregulated in vivo and other calcium homeostasis genes were significantly deregulated in vitro. Genes related to OTA transport (OATs) and metabolism (CYPs) appeared downregulated in vivo. Overall, the mechanism of action of OTA remains unclear, however transcriptomic data have contributed to new mechanistic hypothesis generation and to in vitro-in vivo comparison.
真菌毒素赭曲霉毒素 A（OTA）是雄性大鼠的一种强效肾致癌物。已经综述了关于 OTA 的转录组学研究（4 项体外、6 项体内、2 项体外/体内）。其中 6 项主要是为了研究其作用机制，而其余的主要是为了预测（1 项）或评估（5 项）目的。观察到总体上基因表达下调的趋势，可能是由于蛋白质合成抑制所致。大多数研究中未发现 DNA 损伤反应基因失调。在几项体内研究中，与急性肾损伤、细胞存活和细胞增殖相关的基因上调。凋亡基因在体外失调，但在体内影响较小；已经观察到几种 MAPK 的激活。许多与氧化应激相关的基因或参与细胞间相互作用途径（Wnt）或细胞骨架结构的基因在体外或体内似乎失调。Regucalcin 在体内高度下调，其他钙稳态基因在体外显著失调。与 OTA 转运（OATs）和代谢（CYPs）相关的基因在体内似乎下调。总体而言，OTA 的作用机制仍不清楚，然而转录组学数据有助于提出新的作用机制假说，并进行体外-体内比较。
