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A novel support vector machine-based 1-day, single-dose prediction model of genotoxic hepatocarcinogenicity in rats.
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- Author(s): Gi, Min1,2 (AUTHOR); Suzuki, Shugo2 (AUTHOR); Kanki, Masayuki2 (AUTHOR); Yokohira, Masanao3,4 (AUTHOR); Tsukamoto, Tetsuya5 (AUTHOR); Fujioka, Masaki2 (AUTHOR); Vachiraarunwong, Arpamas1 (AUTHOR); Qiu, Guiyu2 (AUTHOR); Guo, Runjie1 (AUTHOR); Wanibuchi, Hideki2 (AUTHOR)
- Source:
Archives of Toxicology. Aug2024, Vol. 98 Issue 8, p2711-2730. 20p.- Subject Terms:
- Source:
- Additional Information
- Abstract: The development of a rapid and accurate model for determining the genotoxicity and carcinogenicity of chemicals is crucial for effective cancer risk assessment. This study aims to develop a 1-day, single-dose model for identifying genotoxic hepatocarcinogens (GHCs) in rats. Microarray gene expression data from the livers of rats administered a single dose of 58 compounds, including 5 GHCs, was obtained from the Open TG-GATEs database and used for the identification of marker genes and the construction of a predictive classifier to identify GHCs in rats. We identified 10 gene markers commonly responsive to all 5 GHCs and used them to construct a support vector machine-based predictive classifier. In the silico validation using the expression data of the Open TG-GATEs database indicates that this classifier distinguishes GHCs from other compounds with high accuracy. To further assess the model's effectiveness and reliability, we conducted multi-institutional 1-day single oral administration studies on rats. These studies examined 64 compounds, including 23 GHCs, with gene expression data of the marker genes obtained via quantitative PCR 24 h after a single oral administration. Our results demonstrate that qPCR analysis is an effective alternative to microarray analysis. The GHC predictive model showed high accuracy and reliability, achieving a sensitivity of 91% (21/23) and a specificity of 93% (38/41) across multiple validation studies in three institutions. In conclusion, the present 1-day single oral administration model proves to be a reliable and highly sensitive tool for identifying GHCs and is anticipated to be a valuable tool in identifying and screening potential GHCs. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Archives of Toxicology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
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