지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.10
- 수록면
- 289 - 301 (13page)
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초록· 키워드
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Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals. The model was based on short term exposure assays (3 days) and the training was limited to oxidative stressors, peroxisome proliferators and hormone modulators. Validation of the predictor was performed on independent toxicogenomic data (TG-GATEs, Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System, Osaka, Japan). To build our model we performed Random Forests together with a recursive elimination algorithm (VarSelRF). Gene set enrichment analysis was employed for functional interpretation. A total of 770 microarrays comprising 96 different compounds were analyzed and a predictor of 54 genes was built. Prediction accuracy was 0.85 in the training set, 0.87 in the test set and increased with increasing concentration in the validation set: 0.6 at low dose, 0.7 at medium doses and 0.81 at high doses. Pathway analysis revealed gene prominence of cellular respiration, energy production and lipoprotein metabolism. The biggest target of toxicogenomics is accurately predict the toxicity of unknown drugs. In this analysis, we presented a classifier that can predict non-genotoxic carcinogenicity by using short term exposure assays. In this approach, dose level is critical when evaluating chemicals at early time points.
목차
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
참고문헌 (30)
참고문헌 신청
McGovern, T / 2006 / Regulation of genotoxic and carcinogenic impurities in drug substances and products / TrAC, Trends Anal. Chem 25:790~795
Hayashi, Y / 1992 / Overview of genotoxic carcinogens and non-genotoxic carcinogens / Exp. Toxicol. Pathol 44:465~471
Hernández, L. G / 2009 / Mechanisms of non-genotoxic carcinogens and importance of a weight of evidence approach / Mutat. Res 682:94~109
Robinson, J. F / 2012 / A review of toxicogenomic approaches in developmental toxicology / Methods Mol. Biol 889:347~371
National Research Council (US) Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology / 2007 / Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment / National Academies Press
Hayashi, Y / 1992 / Overview of genotoxic carcinogens and non-genotoxic carcinogens / Exp. Toxicol. Pathol 44:465~471
Hernández, L. G / 2009 / Mechanisms of non-genotoxic carcinogens and importance of a weight of evidence approach / Mutat. Res 682:94~109
Robinson, J. F / 2012 / A review of toxicogenomic approaches in developmental toxicology / Methods Mol. Biol 889:347~371
National Research Council (US) Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology / 2007 / Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment / National Academies Press
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UCI(KEPA) : I410-ECN-0101-2017-513-001339552