Toxicogenomic Analyses of Genetic Susceptibility to Mammary Gland Carcinogenesis in Rodents: Implications for Human Breast Cancer

Abstract

The Human Genome Project and the multitude of genomic technologies that it generated have dramatically altered the face of biological research. Genomic sequence information allowed for the development of high throughput technologies for DNA sequencing, gene expression profiling, genotyping, and detection of epigenetic changes. These technologies provide an unprecedented opportunity to elucidate how genetic variation and cellular responses to insult from environment toxicants and stressors, drugs, infections, co-morbid disease, and dietary factors among others, contribute to complex human diseases, including cancer. Toxicogenomics, which combines classical toxicology and genetics with the tools of modern genomics, promises to help elucidate and classify compounds based on mechanisms of toxicity, predict toxicity of untested compounds, provide improved screening and exposure monitoring, enhance the ability to predict toxicity and disease outcomes following exposure, and identify genetically susceptible individuals. Toxicogenomic data are therefore expected to do much to inform risk assessment. Rodents are excellent models for the study of the molecular and genetic bases for human disease, and are still used extensively to screen for toxic effects of drugs and environmental toxicants. In the present review, we explore how the combination of toxicogenomic approaches with rodent models can accelerate the discovery of human breast cancer susceptibility genes.