Comparative Genomic Hybridization (CGH) in Genotoxicology.

In the past two decades, comparative genomic hybridization (CGH) and array CGH have become indispensable tools in clinical diagnostics and toxicological risk assessment. Initially developed for the genome-wide screening of chromosomal imbalances, that is, copy-number variations in tumor cells, both CGH and array CGH have been employed in genotoxicology and most recently in toxicogenomics. The latter allows a multi-end point analysis of how particular genes react to toxic agents, revealing changes in signaling pathways and other underlying molecular mechanisms. This chapter provides background on the use of CGH and array CGH in the context of genotoxicology, and also a protocol for conventional CGH, so that the basic principles of this methodology can be better understood. Conventional and array CGH investigate DNA expression patterns, copy-number variations across the whole genome, and loss of heterozygosity after genotoxic damage. Array CGH is still cost-intensive but produces exponentially more data, requiring suitable analytical algorithms and sophisticated bioinformatic analysis. As toxicogenomics is an emerging sub-discipline of toxicology research, effectively evaluating toxicogenomic microarray data can be hugely advantageous for human risk assessment, even though international regulatory guidelines on toxicogenomics have yet to be fully agreed and implemented.