Grantee Research Project Results
Conformational Protein Effects of Environmental Mutagens
EPA Grant Number: R826685Title: Conformational Protein Effects of Environmental Mutagens
Investigators: Brandt-Rauf, Paul
Institution: Columbia University in the City of New York
EPA Project Officer: Aja, Hayley
Project Period: October 1, 1998 through September 30, 2001
Project Amount: $388,644
RFA: Exploratory Research - Human Health (1998) RFA Text | Recipients Lists
Research Category: Human Health
Description:
The objective of this research is to test the hypothesis that different environmentally induced mutations in the p53 tumor suppressor protein produce common conformational changes in p53 that explain their common carcinogenic effect.
Approach:
Conformational energy analysis and molecular dynamics simulations will be used to determine the three-dimensional structures of eight different p53 mutants produced by four different environmental mutagens.
Expected Results:
The experiments are laboratory based and focus on the characterization of the aerosols through the development of new in situ spectroscopic methods. Measurements as a function of laser fluence are beginning to provide information on (1) the composition of the particles, (2) the partitioning of various species between the two phases, (3) the rates of evaporation of the various species, which in turn will provide information on the layered structure of the particles and (4) the rates of re-equilibration after the heating cycle, providing insights into the uptake of semi-volatiles on short time scales.
Improvement in Risk Assessment or Risk Management: It is expected that the results will identify regions of common conformational change in p53 that can be identified by antibody analysis which could then be used as biomarkers for monitoring the mutagenic effects of environmental mutagens in exposed populations.
Publications and Presentations:
Publications have been submitted on this project: View all 5 publications for this projectJournal Articles:
Journal Articles have been submitted on this project: View all 5 journal articles for this projectSupplemental Keywords:
Health, RFA, Scientific Discipline, Health Risk Assessment, Risk Assessments, Disease & Cumulative Effects, cancer risk, carcinogens, health effects, immunohistochemistry, biological markers, environmental stressors, human exposure, molecular characterization, p53 tumor supressor gene, cancer risk assessment, cell biology, multi-pollutant analyses, indicators, environmentally induced mutations, conformational proteinProgress and Final Reports:
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.