Conformational Protein Effects of Environmental MutagensEPA Grant Number: R826685
Title: Conformational Protein Effects of Environmental Mutagens
Investigators: Brandt-Rauf, Paul
Institution: Columbia University in the City of New York
EPA Project Officer: Hahn, Intaek
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: Health Effects , Human Health , Health
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.
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.
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.