The Utility of Dna Microarrays for 
Characterizing  Genotoxicity

Newton, Ronald K.; Aardema, Marilyn J.; Aubrecht, Jiri

doi:10.1289/txg.6709

Cited by 3 publications

(3 citation statements)

References 17 publications

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“…In agreement with previous studies, there was generally a time-dependent increase in the number of differentially expressed genes. 17,18 Carcinogenic versus non-carcinogenic compounds There were no common genes altered by all of the renal carcinogens (GTX + NGTX), including the three GTX compounds tested in the presence of a S9 metabolising system. However, three genes Mdm2 (MDM2 p53 binding protein), p21 (cyclindependent kinase inhibitor 1) and Cd55 (decay accelerating factor for complement), were commonly altered by 6 out of 9 compounds (67%) in case of Mdm2 and by 5 out of 9 compounds (56%) in case of p21 and Cd55 (Table 3).…”

Section: Transcriptomics Studiesmentioning

confidence: 99%

Detection of genotoxic and non-genotoxic renal carcinogens in vitro in NRK-52E cells using a transcriptomics approach

et al. 2012

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There is a need to develop quick, cheap, sensitive and specific methods to detect the carcinogenic potential of chemicals. Currently there 10 is no in vitro model system for reliable detection of non-genotoxic carcinogens (NGTX) and current tests for detection of genotoxic carcinogens (GTX) can have low specificity. A transcriptomics approach holds promise and a few studies have utilised this technique. However, the majority of these studies have examined liver carcinogens with little work on renal carcinogens which may act via renalspecific NGTX mechanisms. In this study the normal rat renal cell line (NRK-52E) was exposed to sub-toxic concentrations of selected rat renal carcinogens and non-carcinogens (NC) for 6h, 24h and 72h. Renal carcinogens were classified based on their presumed mode of 15 action into GTX and NGTX classes. A whole-genome transcriptomics approach was used to determined genes and pathways as potential signatures for GTX, NGTX and those common to both carcinogenic events in vitro. For some of the GTX compounds an S9 drug metabolising system was included to aid pro-carcinogen activation. Only three genes were deregulated after carcinogen (GTX + NGTX) exposure, one Mdm2 with a detection rate of 67%, and p21 and Cd55 with a detection rate of 56%. However, examination of enriched pathways showed that 3 out of 4 NGTX carcinogens and 4 out of 5 GTX carcinogens were related to known pathways involved in 20 carcinogenesis giving a detection rate of 78%. In contrast, none of the NC chemicals induced any of the above genes or well-established carcinogenic pathways. Additionally, five genes (Lingo1, Hmox1, Ssu72, Lyrm and Usp9x) were commonly altered with 3 out of 4 NGTX carcinogens but not with NC or GTX carcinogens. However, there was no clear separation of GTX and NGTX carcinogens using pathway analysis with several pathways being common to both classes. The findings presented here indicate that the NRK-52E cell line has the potential to detect carcinogenic chemicals, although a much larger number of chemicals need to be used to confirm these 25 findings.

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Section: Transcriptomics Studiesmentioning

confidence: 99%

Detection of genotoxic and non-genotoxic renal carcinogens in vitro in NRK-52E cells using a transcriptomics approach

et al. 2012

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“…Subsequently gene expression levels are also quantified within a single experiment [24][25][26]. Molecules attached to the microarray support (DNA, RNA, oligonucleotides, protein, peptides and tissue fragments) act as sensors [27][28][29] to obtain information on the genome transcription or mutation process [30]. Two important technologies were derived from high density DNA microarray: cDNA microarrays (Stanford University, USA) and "GeneChip" (Affymetrix, CA, USA) [30,31].…”

Section: An Overview Of Microarrays Technologymentioning

confidence: 99%

Microarray and Nanotechnology Applications of Functional Nanoparticles

Pedroso¹,

Guillén

2006

CCHTS

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Microarrays are a sensitive, specific, miniaturized devices that may be used to detect selected DNA sequences and proteins, or mutated genes associated with human diseases. Several methods have been developed to detect the binding of complementary molecules to microarrays by generating an optical signal. One of the most commonly used molecular labeling methods at present is fluorescence, but its application is expensive due to sophisticated equipment required to design the platform, hybridize it, and interpret the images derived from microarray-based studies. This is a drawback for its use in laboratories and clinical services. Another less expensive procedure having similar sensitivity and specificity is DNA and protein functional nanoparticles (FNP). Nanoparticles are sphere-like biocompatible materials made of inert silica, metal or crystals of a nanometer in size, which are generally coated with a thin gold layer. They may be used as hybridization probes in single nucleotide polymorphism (SNP) screening and to detect biological markers for cancer, infection, and cardiovascular diseases.

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“…In related activities, HESI also reviewed the application of genomics to genotoxicity risk assessment [12] . The GADD45a gene family was highlighted amongst the few biologically relevant genes showing robust upregulation (3-to 14-fold) following exposure of cells to direct DNAdamaging agents.…”

Section: Introductionmentioning

confidence: 99%

GADD45a-GFP GreenScreen HC genotoxicity screening assay

Walmsley

2008

Expert Opinion on Drug Metabolism & Toxicology

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Background : Genetic toxicology is getting very interesting. The International Conference on Harmonisation has drafted new guidance that allows for the registration of pharmaceuticals without the submission of data from in vitro mammalian genotoxicity tests ( in vitro micronucleus test, chromosomal aberrations, mouse lymphoma assay). These tests often produce falsely positive predictions of genotoxic carcinogenicity. Objectives : This article reviews the properties of the GADD45a-GFP (green fluorescent protein) assay, for which positive results appear to provide more reliable predictions of genotoxic carcinogenicity. The criteria for assessment of genotoxicity assays are reviewed. Consideration is given to the value of genotoxicity hazard assessment early in pharmaceutical discovery. Methods : Peer-reviewed data have been reviewed, as well as information contributed to the public domain through conference presentations. Results/conclusion : The GADD45a assay is increasingly used as a screening tool, and has utility in the prioritisation of Ames-negative compounds prior to in vivo genotoxicity assessment.

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The Utility of Dna Microarrays for Characterizing Genotoxicity

Cited by 3 publications

References 17 publications

Detection of genotoxic and non-genotoxic renal carcinogens in vitro in NRK-52E cells using a transcriptomics approach

Detection of genotoxic and non-genotoxic renal carcinogens in vitro in NRK-52E cells using a transcriptomics approach

Microarray and Nanotechnology Applications of Functional Nanoparticles

GADD45a-GFP GreenScreen HC genotoxicity screening assay

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