• Publications
  • Influence
Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity.
Results showed that gene expressional profiles for compounds with similar toxic mechanisms indeed formed clusters, suggesting a similar effect on transcription, and show that large-scale analysis of gene expression using microarray technology has promise as a diagnostic tool for toxicology. Expand
Pooling samples within microarray studies: a comparative analysis of rat liver transcription response to prototypical toxicants.
Combining or pooling individual samples when carrying out transcript profiling using microarrays reduced resource requirements substantially, but the individual approach enabled statistical analysis that identified more gene expression changes to evaluate mechanisms of toxicity. Expand
Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles.
The results suggest that microarray assays may prove to be a highly sensitive technique for safety screening of drug candidates and for the classification of environmental toxins. Expand
In silico methods combined with expert knowledge rule out mutagenic potential of pharmaceutical impurities: an industry survey.
To assess how confident the authors can be in identifying non-mutagenic structures, eight companies were surveyed and the Negative Predictive Value (NPV) of the in silico approaches was 94%. Expand
Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens.
Toxicogenomic analysis using short-term studies can be used to identify a threshold for nongenotoxic carcinogens based on evaluation of potential key event(s) which then can be use within a risk assessment framework. Expand
Underlying mechanisms of pharmacology and toxicity of a novel PPAR agonist revealed using rodent and canine hepatocytes.
  • Yin Guo, R. Jolly, +12 authors T. Ryan
  • Biology, Medicine
  • Toxicological sciences : an official journal of…
  • 1 April 2007
Using rat and dog primary hepatocytes, the pharmacologic and toxicologic effects of LY465608 observed in vivo during preclinical development are replicated and an underlying mechanism for these species-specific effects is proposed. Expand
Clofibrate-induced gene expression changes in rat liver: a cross-laboratory analysis using membrane cDNA arrays.
The potential for gene expression profiling to identify toxic hazards by the identification of mechanistically relevant markers of toxicity is demonstrated, and some variability in the quantitative nature of the microarray data is indicated. Expand
Identifying toxic mechanisms using DNA microarrays: evidence that an experimental inhibitor of cell adhesion molecule expression signals through the aryl hydrocarbon nuclear receptor.
It is indicated that A-277249 hepatic toxicity is mediated by the AhR either directly or through effects on NF-kappa B, and the utility of microarray analysis for the rapid identification of toxic hazards for new chemical entities is demonstrated. Expand
Antioxidant-dependent inhibition of diquat-induced toxicity in vivo.
The abilities of two experimental antioxidants, as well as the model antioxidant, diphenyl-p-phenylenediamine (DPPD), to protect against diquat-induced toxicity in male Fischer-344 rats were examined, suggesting that initiation of diqu at-induced hepatotoxicity is rapid and that these compounds would therefore be unlikely to have clinical utility in the treatment ofdiquat intoxication. Expand
The role of transcriptome analysis in pre-clinical toxicology.
This review 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 transcriptomeAnalysis has already begun to have impact. Expand