CARCINOscreen®: New short-term prediction method for hepatocarcinogenicity of chemicals based on hepatic transcript profiling in rats

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  • Matsumoto Hiroshi
    Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan (CERI)
  • Saito Fumiyo
    Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan (CERI)
  • Takeyoshi Masahiro
    Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan (CERI)

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  • CARCINOscreen : New short-term prediction method for hepatocarcinogenicity of chemicals based on hepatic transcript profiling in rats

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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 from68 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 in94.1% 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.

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