Grantee Research Project Results
2003 Progress Report: Screening Disinfection Byproducts (DBPs) for Their Ability To Promote Autoimmunity
EPA Grant Number: R829417E02Title: 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 Period Covered by this Report: May 24, 2003 through May 23, 2004
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)
Objective:
This research project includes 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. In the level one screen, inbred MRL/+ mice will be treated for 4 weeks with trichloroethylene (TCE) CYP2E1 metabolites (i.e., chloral hydrate, trichloroacetic acid, and dichloroacetic acid) in 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. The level two screen will be used 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. An in vitro screening assay will be developed in which flow cytometry will be used to determine whether DBPs upregulate CD44 on CD4+ T cells in vitro.
Progress Summary:
Dr. Sarah Blossom, a postdoctoral fellow supported by this grant, has made excellent progress on this project. She has demonstrated that treatment of MRL+/+ mice with low doses of DBPs in vivo results in the development of immune system alterations commensurate with autoimmune disease. This work has been submitted to the Journal of Autoimmunity. Dr. Blossom also found that in vivo or in vitro exposure to certain DPBs inhibits activation-induced cell death in T-cells, a mechanism that has been shown to promote autoimmune disease. Based on this work, Dr. Blossom has been awarded a travel grant to present her data at the 12th International Congress of Immunology in Montreal in July 2004. In addition, she is examining the mechanism by which DBPs alter T-cell apoptosis. This work is expected to produce some very exciting and novel results. Dr. Kathleen Gilbert recently has published work showing that one of the DBPs described in the grant can promote signaling via Schiff base formation in T-cells in vitro. The connection between T-cell signaling and alterations in T-cell apoptosis is now being explored. Dr. Pumford, our collaborator at the University of Arkansas in Fayetteville, has continued to provide invaluable help with toxicological evaluations of the treated mice, and has recently published a manuscript concerning the ability of toxicants, including DBPs, to promote autoimmune hepatitis in mice.
Future Activities:
We will examine how DBPs alter T-cell apoptosis. In addition, we are in the middle of the long-term study designed to determine how chronic exposure to very low concentrations of DBPs alter immune function, and to delineate DBP-induced autoimmune pathology.
Dr. Blossom was not able to start work in the laboratory until 6 months after the initially designated project start date. Consequently, it is anticipated that the project schedule will need to be extended.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
| Other project views: | All 5 publications | 2 publications in selected types | All 2 journal articles |
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Blossom SJ, Pumford NR, Gilbert KM. Disinfection by-products trichloroacetaldehyde and trichloroacetic acid in the water supply promote T cell activation in mice. Journal of Autoimmunity, 2004. 23(3): 211-220. |
R829417E02 (2002) R829417E02 (2003) |
not available |
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Gilbert KM, Whitlow A, Pumford NR. Environmental contaminant and disinfection by-product trichloroacetaldehyde stimulates T cells in vitro. International Journal of Immunopharmacology 2004;4(1):25-36. |
R829417E02 (2002) R829417E02 (2003) R829417E02 (Final) |
not available |
Supplemental Keywords:
lupus, immunotoxicology, disinfection byproducts, DBPs, autoimmunity, geographic area, health, international cooperation, physical aspects, pollutants/toxics, water, biochemistry, drinking water, environmental chemistry, health risk assessment, physical processes, risk assessments, state, water pollutants, Arkansas, alternative disinfection methods, animal model, autoimmunity, bioindicator, biomarker, chemical byproducts, diagnostic tool, drinking water system, drinking water treatment, ecological risk assessment, environmental risks, exposure, human exposure, human health risk,, Health, RFA, Scientific Discipline, PHYSICAL ASPECTS, INTERNATIONAL COOPERATION, Geographic Area, Water, POLLUTANTS/TOXICS, Health Risk Assessment, Physical Processes, Risk Assessments, State, Environmental Chemistry, Drinking Water, Water Pollutants, ecological risk assessment, water quality, bioindicator, environmental risks, human exposure, animal model, Arkansas, drinking water system, drinking water treatment, exposure, other - risk assessment, autoimmunity, disinfection byproducts, chemical byproducts, diagnostic tool, disinfection byproducts (DPBs), biomarker, human health risk, alternative disinfection methodsProgress and Final Reports:
Original AbstractThe 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.