Kinetic Modeling of Damage Repair, Genome Instability, and Neoplastic Transformation

[摘要] Inducible repair and pathway interactions may fundamentally alter the shape of dose-response curves because different mechanisms may be important under low- and high-dose exposure conditions. However, the significance of these phenomena for risk assessment purposes is an open question. This project developed new modeling tools to study the putative effects of DNA damage induction and repair on higher-level biological endpoints, including cell killing, neoplastic transformation and cancer. The project scope included (1) the development of new approaches to simulate the induction and base excision repair (BER) of DNA damage using Monte Carlo methods and (2) the integration of data from the Monte Carlo simulations with kinetic models for higher-level biological endpoints. Methods of calibrating and testing such multiscale biological simulations were developed. We also developed models to aid in the analysis and interpretation of data from experimental assays, such as the pulsed-field gel electrophoresis (PFGE) assay used to quantity the amount of DNA damage caused by ionizing radiation.

[发布日期] 2007-03-17

[学科分类] 生物科学（综合）

[关键词] CELL KILLING;DNA DAMAGES;ELECTROPHORESIS;EXCISION REPAIR;INDUCTION;INSTABILITY;IONIZING RADIATIONS;KINETICS;MONTE CARLO METHOD;NEOPLASMS;REPAIR;RISK ASSESSMENT;SHAPE;TESTING;TRANSFORMATIONS low dose;radiation b