Screening Disinfection Byproducts (DBPs) for Their Ability To Promote AutoimmunityEPA Grant Number: R829417E02
Title: Screening Disinfection Byproducts (DBPs) for Their Ability To Promote Autoimmunity
Investigators: Gilbert, Kathleen M. , Pumford, Neil R.
Institution: University of Arkansas - Little Rock
EPA Project Officer: Chung, Serena
Project Period: May 24, 2002 through May 23, 2004 (Extended to May 23, 2005)
Project Amount: $250,000
RFA: EPSCoR (Experimental Program to Stimulate Competitive Research) (2001) RFA Text | Recipients Lists
Research Category: EPSCoR (The Experimental Program to Stimulate Competitive Research)
The overall objective of this research project is to use a two-level in vivo screening procedure to directly examine the autoimmune-promoting capacity of disinfection byproducts (DBPs). The specific objectives of this research project are to:
1. Treat inbred MRL/+ mice for 4 weeks with trichloroethylene (TCE) CYP2E1 metabolites (i.e., chloral hydrate, 1,1,2-trichloroethane, and 1,1-dichloroethane) in the drinking water. To determine whether the autoimmune-promoting capacity of DBPs is limited to TCE metabolites, three other DBPs of the halomethane class that have been reported to induce immune system alterations (i.e., chloroform, bromodichloromethane, and chlorodibromomethane) also will be tested. The mice will be examined for serological signs of autoimmune disease, as well as T-cell expression of CD44.
2. Use the level two screen to confirm that two DBPs identified as effective in Objective 1 can induce autoimmune disease and CD4+ T-cell alterations when administered to MRL/+ mice at lower concentrations for a longer time period (40 weeks) because chronic treatment with a low dose of DBPs is probably most relevant to actual environmental exposure.
3. Develop an in vitro screening assay in which flow cytometry will be used to determine whether DBPs upregulate CD44 on CD4+ T cells in vitro.