title: CARCINOscreen®: New short-term prediction method for hepatocarcinogenicity of chemicals based on hepatic transcript profiling in rats.
abstract: Carcinogenicity is one of the most serious toxic effects of chemicals, and highly accurate methods for predicting carcinogens are strongly desired for human health. Here, we developed a new prediction system named "CARCINOscreen®" for evaluating the carcinogenic potentials of chemicals using the gene expression profiles of liver tissues from rats after a 28-day repeated dose toxicity study.The prediction formula was generated using a support vector machine with predictive genes selected from 68 training chemical datasets; a predictive score was then calculated to predict the carcinogenic potentials of the tested chemicals. To ensure the accuracy of the prediction system, the chemicals were divided into three groups (Groups 1 to 3) according to the resulting hepatic gene expression profiles, and a prediction formula was generated for each group. The prediction system was capable of predicting the carcinogenicity of training carcinogens and non-carcinogens with an accuracy of 92.9% to 100%. The final prediction result was determined based on the maximum prediction value obtained with three independent prediction formulas to build up the CARCINOscreen®. The system was able to predict carcinogenicity accurately in 94.1% of the 68 training chemicals. An external validation trial was performed with 16 chemicals, consisting of various carcinogens targeting rat liver or other organs and non-carcinogens. The system identified 68.8% of all the chemicals and 100% of the rat liver carcinogens as carcinogens. Thus, the CARCINOscreen®, a novel system for predicting hepatocarcinogenicity, is a promising tool for the prediction of rat liver carcinogens.
authors.affiliation: Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan (CERI).
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Saito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeyoshi
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000633:toxicity*; D020869:Gene Expression Profiling / Q000379:methods*; D008099:Liver / Q000187:drug effects*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity
chemical_list: D002273:Carcinogens