Table 2 summarizes some of the opportunities for improved toxicological assessment created by the advances in molecular technologies and our enhanced knowledge of the molecular basis of tissue damage and response. These include opportunities for improved biomarkers, better technologies for monitoring biomarkers, and new laboratory models that incorporate human biochemical characteristics. Examples of implementation of each of these opportunities already exist. The discussion below focuses on the impact of the recent revolution in genetics and biotechnology on strategies for improved biomarker development and application, and on assessment of the role of genetic variation in determining or modifying toxicological outcomes.
New technologies of molecular biology are being applied in several ways to assess the function and structure of the major organ and tissue systems. Much attention is currently focused on the potential of DNA microarrays to identify either inducible damage responses or shifts in genetic expression patterns that are characteristic of specific molecular insults to the cell. This focus is driven by the convergence of two factors: (1) the availability of technology to monitor the expression of many genes simultaneously using very small samples of DNA or RNA, and (2) the recently developed knowledge that molecular evolution has resulted in specific inducible defense systems and regulatory control pathways for key cell functions. Additional opportunities include the potential (1) to develop comprehensive panels of biomarkers of cell and tissue integrity through proteomic technologies, (2) for monitoring functional pathways using metabonomic technologies, (3) for development of mechanism-based models of human disease (including short-term models of carcinogenesis), (4) to identify genetic alterations that lead to human disease, and (5) for application of imaging technologies to noninvasive monitoring. Each of these opportunities merits discussion.