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

Technical Report · Sat Mar 17 00:00:00 EDT 2007

DOI:https://doi.org/10.2172/900981· OSTI ID:900981

Stewart, Robert D

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.

• Research Organization: Purdue University, West Lafayette, IN
• Sponsoring Organization: USDOE Office of Science (SC)
• DOE Contract Number: FG02-03ER63541
• OSTI ID: 900981
• Report Number(s): DOE/03ER63541; Purdue Reference Number 541 1338-0220; TRN: US200821%%302
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
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 biology
modeling
DNA damage
DNA repair
genomic instability
cell killing
cell transformation