title: Simpler alternative to CARCINOscreen(®) based on quantitative PCR (qPCR).
abstract: Carcinogenicity of chemicals in our environment is one of the most important health hazards to humans. Recently, a microarray-based short-term prediction system for the hepatocarcinogenicity of chemicals, named CARCINOscreen(®), was developed. Although the system is a promising tool reported to have an ability to predict hepatocarcinogenicity in rats with 92.9% accuracy, it requires specialized equipment and skilled bioinformatics approaches for data analysis. Therefore, we attempted to develop a quantitative PCR (qPCR)-based system as an alternative to microarray-based CARCINOscreen(®). Finally, an optimized gene set consisting of four predictive genes (Abcb1b, Eprs, Map3K8, and Igh-6) was selected from among 3,150 combinations of candidate gene sets. The results of training- and validation-phase trials showed that the qPCR-based alternative to the microarray-based CARCINOscreen(®) could predict the hepatocarcinogenicity of chemicals in rats with 82.8%-86.4% accuracy. One of the predictive genes, Abcb1b, a member of the ATP-binding cassette protein superfamily and multi-drug resistance-associated protein, and the results of this study may indicate a close relation of this gene to the carcinogenicity of chemicals. The prediction performance of the qPCR-based CARCINOscreen(®), as well as its user-friendliness and cost efficiency, suggests that this method is promising for application to primary health hazard assessment. Thus, the qPCR-based CARCINOscreen(®) is considered as a promising tool for predicting the carcinogenicity of chemicals.
authors.affiliation: Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan (CERI).
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Akahori
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeyoshi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015197:Carcinogenicity Tests / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D050438:Genes, Immunoglobulin Heavy Chain; D059014:High-Throughput Nucleotide Sequencing; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D018570:Risk Assessment
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; C095122:multidrug resistance protein 3; D020930:MAP Kinase Kinase Kinases; C080356:Map3k8 protein, rat; D000604:Amino Acyl-tRNA Synthetases; C415462:glutamyl-prolyl-tRNA synthetase