Novel and future applications of microarrays in toxicological research

Abstract

Abstract.Microarray technologies have both fascinated and frustrated the toxicological community since their introduction about a decade ago. Fascination arose from the possibility offered by the technology to gain a profound incite into the cellular response to chemically mediated stress, and the potential that this genomic signature would be indicative of the biological mechanism by which that stress was induced.Frustrations have arisen primarily from technical factors such as data variance, the requirement for the application of advanced statistical and mathematical analysis and difficulties associated with actually recognising signature gene expression patterns, and discerning mechanisms. Toxicogenomics was predicted to make toxicological assessment and extrapolation easier, faster and cheaper. The reality has been that toxicogenomics is difficult. However, its potential when properly applied has been indicated by some well designed toxicogenomics studies, particularly in the differentiation of genotoxins from non-genotoxins. Technology waits though for no man. While the toxicological community has been working to apply transcriptomics (mRNA levels) in toxicology the technology has moved beyond this application into new arenas. Some have application to toxicology and are reviewed here, except transcriptomics which has been extensively written about before. Discussed are the application of microarray technologies applied to the genome per se (amplifications, deletions, epigenetic change), mRNA translation and its control mechanisms through miRNA. Which of the new genomics technologies will find most application in toxicology? In the opinion of this author there are three potentially major applications; 1) ArrayCGH in assessment and recognition of genotoxicity, 2) epigenetic assessment in developmental and transgenerational toxicology and, 3) miRNA assessment in all toxicology types but in particular developmental toxicology.

Induction of gene pattern changes associated with dysfunctional lipid metabolism induced by dietary fat and exposure to a persistent organic pollutant

“…It is therefore likely that there is a link between environmental risk factors such as nutrition and exposure to environmental pollutants on overall disease outcome (Hennig et al 2005a). Evolving genomic tools and technologies, including DNA microarray analysis, offer opportunities to gain insight into the cellular response to interactions of nutrition and toxicology on induction of cellular stress and biological mechanisms involved in these biological phenomena (Spielbauer et al 2005; Gant 2007). DNA microarray technology allows simultaneous measurement of mRNA expression levels from thousands of genes providing a snapshot of the molecular events associated with perturbation of a biological system.…”

Myocardial toxicity induced by silica nanoparticles in a transcriptome profile

“…With the deepening of research, the -omic technologies manifested more efficiently in mechanistic toxicological investigations, which would promise new insights into mechanisms of NPs action and toxicity. 38,39 In view of the wholegenome expression profiling providing the most comprehensive picture of steady-state levels of transcripts, 40,41 Affymetrix GeneChips was applied to obtain the highly sensitive and informative markers underlying SiNPs' cardiotoxicity. 42 As a result, 1916 down-regulated and 1273 up-regulated DEGs were found after SiNPs exposure.…”

Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives

“…Microarrays are a widely used, high-throughput hybridization-based technology capable of simultaneously detecting the expression of thousands of miRNAs within samples (Liu et al 2008). However, microarrays cannot be used as an absolute quantification method for miRNAs and have lower sensitivity and specificity than qRT-PCR (Gant 2007). A short length and similar sequence among clusters of miR-NAs also influence microarrays.…”