title: New short term prediction method for chemical carcinogenicity by hepatic transcript profiling following 28-day toxicity tests in rats.
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.
authors.affiliation: Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan, 1600 Shimotakano, Sugito-machi, Kitakatsushika-gun, Saitama 345-0043, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Yakabe
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Saito
authors.forename: Koichi
authors.initials: K
authors.lastname: Saito
authors.forename: Kayo
authors.initials: K
authors.lastname: Sumida
authors.forename: Masaru
authors.initials: M
authors.lastname: Sekijima
authors.forename: Koji
authors.initials: K
authors.lastname: Nakayama
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyaura
authors.forename: Masanori
authors.initials: M
authors.lastname: Otsuka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
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