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Special Issue "Toxicogenomics"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 April 2011)

Special Issue Editor

Guest Editor
Dr. Chris Vulpe (Website)

Agricultural Experiment Station, Nutritional Sciences & Toxicology, 119 Morgan Hall #3104, University of California, Berkeley, CA 94720-3104, USA

Special Issue Information

Dear Colleagues,

Current toxicity testing protocols are limited in the number of compounds that can be assessed, and so there are a multitude of chemical compounds found in the environment for which there are no toxicity data. Toxicogenomics, the study of the interaction between the genome, proteome or metabolome and adverse biological endpoints due to exposure to toxicants, provides a means to generate toxicity data for a large number of compounds in a short time. Toxicogenomic studies can also provide insight into the modes of toxicity of compounds, and can allow the identification of susceptibility and exposure biomarkers. All such data can be integrated to give an improved assessment of the toxic potential of an untested compound.

This special issue will consider research and review articles concerning any aspects of toxicogenomics. Studies focusing on emerging concerns in toxicology such as nanotoxicology and epigenetic toxicity are particularly encouraged.

Dr. Chris Vulpe
Guest Editor

Keywords

  • drug discovery
  • ecotoxicology
  • ecotoxicogenomics
  • epigenetic toxicity
  • pitoxicogenomics
  • functional toxicogenomics
  • high-throughput compound screening
  • nanotoxicology
  • systems toxicology
  • toxicity pathways

Published Papers (3 papers)

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Research

Open AccessArticle High-Density Real-Time PCR-Based in Vivo Toxicogenomic Screen to Predict Organ-Specific Toxicity
Int. J. Mol. Sci. 2011, 12(9), 6116-6134; doi:10.3390/ijms12096116
Received: 29 April 2011 / Revised: 24 August 2011 / Accepted: 5 September 2011 / Published: 19 September 2011
Cited by 10 | PDF Full-text (385 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present [...] Read more.
Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study our objective was to extend in vivo toxicogenomic screening from analyzing one or a few tissues to multiple organs, including heart, kidney, brain, liver and spleen. Nanocapillary quantitative real-time PCR (QRT-PCR) was used in the study, due to its higher throughput, sensitivity and reproducibility, and larger dynamic range compared to DNA microarray technologies. Based on previous data, 56 gene markers were selected coding for proteins with different functions, such as proteins for acute phase response, inflammation, oxidative stress, metabolic processes, heat-shock response, cell cycle/apoptosis regulation and enzymes which are involved in detoxification. Some of the marker genes are specific to certain organs, and some of them are general indicators of toxicity in multiple organs. Utility of the nanocapillary QRT-PCR platform was demonstrated by screening different references, as well as discovery of drug-like compounds for their gene expression profiles in different organs of treated mice in an acute experiment. For each compound, 896 QRT-PCR were done: four organs were used from each of the treated four animals to monitor the relative expression of 56 genes. Based on expression data of the discovery gene set of toxicology biomarkers the cardio- and nephrotoxicity of doxorubicin and sulfasalazin, the hepato- and nephrotoxicity of rotenone, dihydrocoumarin and aniline, and the liver toxicity of 2,4-diaminotoluene could be confirmed. The acute heart and kidney toxicity of the active metabolite SN-38 from its less toxic prodrug, irinotecan could be differentiated, and two novel gene markers for hormone replacement therapy were identified, namely fabp4 and pparg, which were down-regulated by estradiol treatment. Full article
(This article belongs to the Special Issue Toxicogenomics)
Figures

Open AccessArticle Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs
Int. J. Mol. Sci. 2011, 12(7), 4609-4624; doi:10.3390/ijms12074609
Received: 7 April 2011 / Revised: 25 May 2011 / Accepted: 12 July 2011 / Published: 15 July 2011
Cited by 6 | PDF Full-text (387 KB) | HTML Full-text | XML Full-text
Abstract
Drug-induced liver injury (DILI) is the primary adverse event that results in the withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in the pre-clinical or clinical phases of drug development. This paper presents an [...] Read more.
Drug-induced liver injury (DILI) is the primary adverse event that results in the withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in the pre-clinical or clinical phases of drug development. This paper presents an approach for identifying potential liver toxicity genomic biomarkers from a liver toxicity biomarker study involving the paired compounds entacapone (“non-liver toxic drug”) and tolcapone (“hepatotoxic drug”). Molecular analysis of the rat liver and plasma samples, combined with statistical analysis, revealed many similarities and differences between the in vivo biochemical effects of the two drugs. Six hundred and ninety-five genes and 61 pathways were selected based on the classification scheme. Of the 61 pathways, 5 were specific to treatment with tolcapone. Two of the 12 animals in the tolcapone group were found to have high ALT, AST, or TBIL levels. The gene Vars2 (valyl-tRNA synthetase 2) was identified in both animals and the pathway to which it belongs, the aminoacyl-tRNA biosynthesis pathway, was one of the three most significant tolcapone-specific pathways identified. Full article
(This article belongs to the Special Issue Toxicogenomics)
Open AccessArticle Global Transcriptomic Profiling Using Small Volumes of Whole Blood: A Cost-Effective Method for Translational Genomic Biomarker Identification in Small Animals
Int. J. Mol. Sci. 2011, 12(4), 2502-2517; doi:10.3390/ijms12042502
Received: 2 March 2011 / Revised: 28 March 2011 / Accepted: 1 April 2011 / Published: 13 April 2011
Cited by 3 | PDF Full-text (291 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Blood is an ideal tissue for the identification of novel genomic biomarkers for toxicity or efficacy. However, using blood for transcriptomic profiling presents significant technical challenges due to the transcriptomic changes induced by ex vivo handling and the interference of highly abundant [...] Read more.
Blood is an ideal tissue for the identification of novel genomic biomarkers for toxicity or efficacy. However, using blood for transcriptomic profiling presents significant technical challenges due to the transcriptomic changes induced by ex vivo handling and the interference of highly abundant globin mRNA. Most whole blood RNA stabilization and isolation methods also require significant volumes of blood, limiting their effective use in small animal species, such as rodents. To overcome these challenges, a QIAzol-based RNA stabilization and isolation method (QSI) was developed to isolate sufficient amounts of high quality total RNA from 25 to 500 μL of rat whole blood. The method was compared to the standard PAXgene Blood RNA System using blood collected from rats exposed to saline or lipopolysaccharide (LPS). The QSI method yielded an average of 54 ng total RNA per μL of rat whole blood with an average RNA Integrity Number (RIN) of 9, a performance comparable with the standard PAXgene method. Total RNA samples were further processed using the NuGEN Ovation Whole Blood Solution system and cDNA was hybridized to Affymetrix Rat Genome 230 2.0 Arrays. The microarray QC parameters using RNA isolated with the QSI method were within the acceptable range for microarray analysis. The transcriptomic profiles were highly correlated with those using RNA isolated with the PAXgene method and were consistent with expected LPS-induced inflammatory responses. The present study demonstrated that the QSI method coupled with NuGEN Ovation Whole Blood Solution system is cost-effective and particularly suitable for transcriptomic profiling of minimal volumes of whole blood, typical of those obtained with small animal species. Full article
(This article belongs to the Special Issue Toxicogenomics)

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