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MECHANISTIC DATA & CANCER RISK ASSESSMENT: THE NEED FOR QUANTITATIVE MOLECULAR ENDPOINTS
Citation:
Preston, R J. MECHANISTIC DATA & CANCER RISK ASSESSMENT: THE NEED FOR QUANTITATIVE MOLECULAR ENDPOINTS. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS. Wiley Liss, New York, NY, 45(2-3):214-221, (2005).
Description:
The cancer risk assessment process as currently proposed by the U.S. Environmental Protection Agency allows for the use of mechanistic data to inform the low dose tumor response in humans and in laboratory animals. The aim is to reduce the reliance on defaults that introduce a relatively high level of uncertainty to the risk estimates. The types of data required for this purpose are those that help identify key events in tumor formation following exposure to environmental chemicals. Informative biomarkers of tumor responses could then be developed for providing a qualitative (form of curve) and quantitative (tumor frequency) description of the low-dose tumor response. A number of recently developed molecular approaches could aid in the development of qualitatively and quantitatively informative biomarkers. An overview of these with examples of their use is presented. These methods include quantitative gene expression array techniques, quantitative proteomic assays and the assessment of DNA alterations at the single gene level and at the genome level of detection. It is most likely that a combination of approaches at these different levels of cellular organization (i.e. RNA, protein and DNA) will be the most productive for biomarker development. The rapid progress that is being made will make the data generated even more readily incorporable into the cancer risk assessment process.