Genotoxicity biomarkers

Toxicogenomic studies in relation to genetic toxicology utilize the comprehensive gene expression data to identify gene expression signatures that strongly correlate with genetic toxicity. The use of these approaches has a long history and only in the past decade, due to rapid development in gene expression technologies such as microarrays, real-time PCR, RNA sequencing, and other bioinformatics tools, has the field of toxicogenomics emerged as an area that may have immense potential for genotoxicity testing. In toxicogenomic studies, changes in gene expression patterns in response to genotoxic stress are most commonly studied, but changes in protein expression or metabolite formation can also be investigated. In addition, toxicogenomic approaches have the potential to overcome some of the limitations posed by traditional genotoxicity testing approaches, such as use of a limited number of animals, especially when changes in a limited set of genes are being investigated. Also, toxicogenomic approaches are more amenable for high throughput and high content screening than are traditional methods, thus aiding in reducing the costs associated with genetic toxicity screening and risk assessment.

Several investigators to date have reported different toxicogenomic signatures both in vitro using rodent and human cancer cell lines and in vivo in rodent models, to predict carcinogenicity in rodents and/or in humans (Thybaud et al., 2007; Ellinger-Ziegelbauer et al., 2009; Fielden et al., 2011). Although toxicogenomic signatures have been proposed to differentiate genotoxins vs. nongenotoxins, aneugens vs. clastogens, carcinogens vs. noncarcinogens, genotoxic carcinogens vs. nongenotoxic carcinogens, etc., no general consensus exists on their usage in genetic toxicology testing. This is primarily because of diverse test models, and gene expression analysis and bioinformatics technologies used to arrive at these toxicogenomic signatures, independently by different groups. To address these challenges, genetic toxicologists across industry, academia, and government are forming consortia (e.g. Health and Environmental Science Institute (HESI) Genomics technical committee, Safety Prediction consortia) to identify and validate unique toxicogenomic signatures that can be utilized for identifying different classes of genotoxins, and for hazard identification and risk assessment.

Regards

Jun Ray

Assistant Mnaging Editor

Environmental Toxicology and Studies Journal