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New Short Term Prediction Method for Chemical Carcinogenicity by Hepatic Transcript Profiling Following 28-Day Toxicity Tests in Rats

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688 Article Views

Publication Date: 27 Oct 2011

Journal: Cancer Informatics

Citation: Cancer Informatics 2011:10 259-271

doi: 10.4137/CIN.S7789

CI journal

637,139 Article Views

7,185,333 Libertas Article Views

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Abstract

We have previously shown the hepatic gene expression profiles of carcinogens in 28-day toxicity tests were clustered into three major groups (Group-1 to 3). Here, we developed a new prediction method for Group-1 carcinogens which consist mainly of genotoxic rat hepatocarcinogens. The prediction formula was generated by a support vector machine using 5 selected genes as the predictive genes and predictive score was introduced to judge carcinogenicity. It correctly predicted the carcinogenicity of all 17 Group-1 chemicals and 22 of 24 non-carcinogens regardless of genotoxicity. In the dose-response study, the prediction score was altered from negative to positive as the dose increased, indicating that the characteristic gene expression profile emerged over a range of carcinogen-specific doses. We conclude that the prediction formula can quantitatively predict the carcinogenicity of Group-1 carcinogens. The same method may be applied to other groups of carcinogens to build a total system for prediction of carcinogenicity.


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