skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

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.

Authors:
Publication Date:
Research Org.:
Purdue University, West Lafayette, IN
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
900981
Report Number(s):
DOE/03ER63541
Purdue Reference Number 541 1338-0220; TRN: US200821%%302
DOE Contract Number:  
FG02-03ER63541
Resource Type:
Technical Report
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

Stewart, Robert D. Kinetic Modeling of Damage Repair, Genome Instability, and Neoplastic Transformation. United States: N. p., 2007. Web. doi:10.2172/900981.
Stewart, Robert D. Kinetic Modeling of Damage Repair, Genome Instability, and Neoplastic Transformation. United States. doi:10.2172/900981.
Stewart, Robert D. Sat . "Kinetic Modeling of Damage Repair, Genome Instability, and Neoplastic Transformation". United States. doi:10.2172/900981. https://www.osti.gov/servlets/purl/900981.
@article{osti_900981,
title = {Kinetic Modeling of Damage Repair, Genome Instability, and Neoplastic Transformation},
author = {Stewart, Robert D},
abstractNote = {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.},
doi = {10.2172/900981},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Sat Mar 17 00:00:00 EDT 2007},
month = {Sat Mar 17 00:00:00 EDT 2007}
}

Technical Report:

Save / Share: