Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen®.

Abstract

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.