Matsumoto Hiroshi, Saito Fumiyo, Takeyoshi Masahiro
Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan (CERI).
J Toxicol Sci. 2015 Dec;40(6):805-7. doi: 10.2131/jts.40.805.
Recently, the development of several gene expression-based prediction methods has been attempted in the fields of toxicology. CARCINOscreen® is a gene expression-based screening method to predict carcinogenicity of chemicals which target the liver with high accuracy. In this study, we investigated the applicability of the gene expression-based screening method to SD and Wistar rats by using CARCINOscreen®, originally developed with F344 rats, with two carcinogens, 2,4-diaminotoluen and thioacetamide, and two non-carcinogens, 2,6-diaminotoluen and sodium benzoate. After the 28-day repeated dose test was conducted with each chemical in SD and Wistar rats, microarray analysis was performed using total RNA extracted from each liver. Obtained gene expression data were applied to CARCINOscreen®. Predictive scores obtained by the CARCINOscreen® for known carcinogens were > 2 in all strains of rats, while non-carcinogens gave prediction scores below 0.5. These results suggested that the gene expression based screening method, CARCINOscreen®, can be applied to SD and Wistar rats, widely used strains in toxicological studies, by setting of an appropriate boundary line of prediction score to classify the chemicals into carcinogens and non-carcinogens.
最近，毒理学领域已尝试开发几种基于基因表达的预测方法。CARCINOscreen®是一种基于基因表达的筛选方法，可高精度预测针对肝脏的化学物质的致癌性。在本研究中，我们通过使用最初针对F344大鼠开发的CARCINOscreen®，对两种致癌物2,4 - 二氨基甲苯和硫代乙酰胺，以及两种非致癌物2,6 - 二氨基甲苯和苯甲酸钠，研究了基于基因表达的筛选方法对SD大鼠和Wistar大鼠的适用性。在用每种化学物质对SD大鼠和Wistar大鼠进行28天重复剂量试验后，使用从每个肝脏中提取的总RNA进行微阵列分析。将获得的基因表达数据应用于CARCINOscreen®。CARCINOscreen®对已知致癌物获得的预测分数在所有大鼠品系中均> 2，而非致癌物的预测分数低于0.5。这些结果表明，通过设置适当的预测分数边界线以将化学物质分类为致癌物和非致癌物，基于基因表达的筛选方法CARCINOscreen®可应用于毒理学研究中广泛使用的品系SD大鼠和Wistar大鼠。
