Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

Huang, Qihong; Jin, Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D; Stoltz, J. H.; Jayadev, Supriya; Blanchard, Kerry T.

doi:10.1016/j.mrfmmm.2003.12.020

Cited by 88 publications

(22 citation statements)

References 34 publications

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“…In in vivo studies, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents [35]. Sprague-Dawley rats were orally treated with acetaminophen, and hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs).…”

Section: The Power Of Toxicogenomicsmentioning

confidence: 99%

Toxicogenomics — A novel opportunity to probe lupus susceptibility and pathogenesis

Tsay

Zouali

2008

International Immunopharmacology

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Section: The Power Of Toxicogenomicsmentioning

confidence: 99%

Toxicogenomics — A novel opportunity to probe lupus susceptibility and pathogenesis

Tsay

Zouali

2008

International Immunopharmacology

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“…There are a number of other recent examples where transcript profiling has played a significant role in the identification of potential toxicity biomarkers [56][57][58][59]. In order to provide continuing benefit in the drug safety assessment process, the more difficult, but necessary step, is the development and implementation of the biomarker as a pre-clinical surrogate screen or as a marker for monitoring patients in a clinical setting [22].…”

Section: Transcriptome Analysis Use In Toxicity Biomarker Identificationmentioning

confidence: 99%

The Role of Transcriptome Analysis in Pre-Clinical Toxicology

Searfoss

Ryan²,

Jolly³

2005

CMM

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A major benefit of the genomics revolution in biomedical research has been the establishment of transcriptome analysis as an enabling technology in the drug development process. Nowhere in the realm of drug development has the expectation of the impact of transcriptome analysis been greater than in the area of pre-clinical toxicology. Transcriptome analysis, along with other new high-content data generating technologies, has the potential to radically improve the drug safety assessment process by allowing drug development teams to identify potential toxicity liabilities earlier, and thus proceed only with those molecules that have both efficacy at the target and a low potential for toxicity in the human population. In this review we will briefly describe the major ways in which transcriptome analysis is being applied in the pre-clinical safety assessment process, focusing primarily on four areas where transcriptome analysis has already begun to have impact. These include using transcriptome analysis to: 1) understand mechanisms of toxicity: 2) predict toxicity: 3) develop in vivo and in vitro surrogate models and screens; and, 4) develop toxicity biomarkers. We will close by briefly addressing future trends and needs in the application of transcriptome analysis to drug safety assessment.

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“…Gene expression analysis has become a widely used approach to identify biomarkers and understand mechanisms of toxicity (Searfoss et al 2003;Bailey and Ulrich 2004;Huang et al 2004). Among the toxicological processes that can be investigated is cell proliferation, which plays an important role in carcinogenesis.…”

Section: Toxicogenomics: Quantification Of Gene Expressionmentioning

confidence: 99%

TaqMan Applications in Genetic and Molecular Toxicology

Watson

2005

Int J Toxicol

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Quantification of nucleic acids has become a common procedure in many toxicology laboratories. Among the technologies that accomplish this is the fluorogenic 5'-nuclease assay, commonly known as TaqMan. Three TaqMan applications for genetic and molecular toxicology are presented in this article: quantification of gene expression, detection of genetic polymorphisms, and quantification of chromosomal DNA deletions. Of these, quantification of gene expression is the most widely used, and established TaqMan as a benchmark technology for nucleic acid quantification. Two additional applications, polymorphism detection and quantification of DNA deletions, demonstrate the flexibility and quantitative strengths that make TaqMan so powerful, including high precision, excellent sensitivity, and broad linear dynamic range. These and similar applications improve our ability to investigate genetic and molecular dimensions of toxicological phenomena, and have promoted the widespread use of TaqMan in toxicology departments in the pharmaceutical industry. In addition to presenting these applications, the authors discuss some of the challenges of integrating TaqMan and other new technologies into the drug development process.

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Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

Cited by 88 publications

References 34 publications

Toxicogenomics — A novel opportunity to probe lupus susceptibility and pathogenesis

Toxicogenomics — A novel opportunity to probe lupus susceptibility and pathogenesis

The Role of Transcriptome Analysis in Pre-Clinical Toxicology

TaqMan Applications in Genetic and Molecular Toxicology

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