Recent advances in understanding/assessing toxicity to the epigenome [version 1; referees: 2 approved]

Abstract

The ability of non-genotoxic agents to induce cancer has been documented and clearly requires a reassessment of testing for environmental and human safety. Drug safety testing has historically relied on test batteries designed to detect DNA damage leading to mutation and cancer. The standard genetic toxicology testing battery has been a reliable tool set to identify small molecules/chemicals as hazards that could lead to genetic changes in organisms and induction of cancer. While pharmaceutical companies and regulatory agencies have extensively used the standard battery, it is not suitable for compounds that may induce epigenetic changes. Additionally, many pharmaceutical companies have changed their product portfolios to include peptides and/or other biological molecules, which are not expected to be genotoxic in their own right. If we are to best use our growing knowledge regarding chemicals and biomolecules that induce heritable changes via epigenetic mechanisms, then we must ask what changes may be needed in our testing paradigm to predict long-term downstream effects through epigenetic mechanisms.

Keywords

• Animal Genetics
• Control of Gene Expression
• Evolutionary/Comparative Genetics
• Medical Genetics
• Toxicology