Grantee Research Project Results
2000 Progress Report: Immunotoxicity of Both Nondegraded and Biodegraded Polychlorinated Biphenyls (PCBs)
EPA Grant Number: R826687Title: Immunotoxicity of Both Nondegraded and Biodegraded Polychlorinated Biphenyls (PCBs)
Investigators: London, Lucille
Current Investigators: London, Lucille , Smithwick, Laura Ashley , Quensen, John , Morris, Pamela
Institution: Medical University of South Carolina
EPA Project Officer: Aja, Hayley
Project Period: September 15, 1998 through September 14, 2001
Project Period Covered by this Report: September 15, 1999 through September 14, 2000
Project Amount: $379,176
RFA: Exploratory Research - Human Health (1998) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The long-term goal of our laboratory is to understand the biological process by which complex mixtures of contaminants can be degraded in the environment and to apply that knowledge to better understand potential human health effects associated with exposure. We have focused on the biodegradation polychlorinated biphenyls (PCBs) and their subsequent immunotoxicological effects. The persistence of PCBs in the environment and their bioaccumulation in living organisms raises concerns regarding their immunotoxic potential and subsequent effects on health. In this proposal, we will examine the immunotoxicity of PCBs and their biodegraded products using a well-defined immunologic parameter as an indicator of immunotoxicity. We will assess both non-degraded and biodegraded (aerobic biodegradation and anaerobic dechlorination) PCBs on their ability to modulate the murine B cell proliferative response to the mitogen, lipopolysaccaride (LPS). We will also investigate the ability of PCBs and their biodegraded/dechlorinated products to modulate immunoglobulin secretion in vitro after LPS stimulation.Progress Summary:
In initial studies, four commercial PCB mixtures (Aroclors) or six individual PCB congeners were evaluated for their effect on splenocyte viability and lipopolysaccharide (LPS)-induced splenocyte proliferation in vitro in two strains of mice, C57Bl/6 (high affinity aromatic hydrocarbon receptor (AhR) complex) and DBA/J (low affinity AhR complex). All four Aroclors, the selected individual noncoplanar congeners, or two tertiary mixtures containing one congener from each class significantly decreased the in vitro LPS-induced proliferation of murine splenocytes in either strain of mice without inducing a significant decrease in viability. In contrast, selected individual coplanar or mono-ortho-coplanar congeners did not inhibit splenocyte proliferation or viability at any concentration. These results suggest that mixtures of PCBs and/or congener class (specifically, noncoplanar congeners) may be more highly immunotoxic than individual planar or mono-ortho-coplanar congeners alone. This is significant since PCB mixtures, not individual congeners, were used industrially and now contaminate the environment. In addition, with respect to human toxicity, only those congeners that bioaccumulate have the potential to influence human health. Our results implicating noncoplanar congeners as potentially immunotoxic are significant since these congeners selectively bioaccumulate and traditional means of assessing toxicity based on TEQ values may underestimate their importance. To follow up on these results, we have observed significant inhibition of LPS-induced proliferation of splenocytes by a number of additional noncoplanar congeners regardless of their chlorine content that have been shown to bioaccumulate in human milk. Only the noncoplanar congeners, regardless of their chlorine content, exhibited a toxic effect on the ability of splenocytes to proliferate in response to LPS. These results are consistent with the toxic effects observed with noncoplanar congeners in a variety of biological systems including effects on neurotoxicity, neutrophil function, and insulin release, among others. Also of importance is the microbial reductive dechlorination of PCBs, which occurs in most PCB-contaminated anaerobic sedimentary environments. This process often results in the accumulation of ortho-substituted PCB congeners. Therefore, there is a general decrease (after dechlorination) in coplanar (dioxin-like congeners) and an increase in mono- and di-ortho-substituted noncoplanar congeners. To examine the toxicity of dechlorinated PCBs, we have established PCB dechlorinating cultures capable of generating dechlorinated Aroclor mixtures for toxicity testing. Substantial dechlorination of Aroclors 1242, 1254, and 1260 was achieved by microorganisms eluted from Cooper River sediments (Charleston, SC) amended with 1,000 ppm Aroclor and 2.5 mM sodium acetate. Interestingly, these enrichment cultures seem to have a preference for the more heavily dechlorinated PCB mixture, Aroclor 1260, which averages just over six chlorines per biphenyl molecule. We are currently in the process of conducting congener-specific analysis of these samples in order to determine the mole percent of each congener and the average number of meta and para chlorines present compared to the parent (undechlorinated) Aroclor. Approximately 90 mg of each dechlorinated Aroclor is presently available for toxicity testing. In addition, ortho- and non-ortho- congeners were successfully separated from Aroclor 1242 using an activated charcoal column, and distinct congener profiles were obtained. This demonstrates our ability to remove coplanar congeners from Aroclor 1242 and to provide two fractions of the parent Aroclor (and dechlorinated Aroclors) to examine in toxicity studies.Future Activities:
The majority of this past year was spent developing, on a large scale, both aerobic and anaerobic PCB degrading cultures which would generate samples with different PCB congener profiles. We plan on evaluating these cultures over the next year with a keen eye on the noncoplanar toxicity issue.
- Determine whether exposure to the various Aroclor mixtures (parent and modified) and various individual PCB congeners (coplanar, mono-ortho-coplanar, noncoplanar) modulate the ability of LPS stimulated B cells to either proliferate or secrete immunoglobulin, the key function of B cells.
- Determine whether the ability of PCBs to modulate either B cell proliferation or immunoglobulin secretion is mediated through a calcium dependent mechanism.
- We will continue to investigate the effect of anaerobic dechlorination of Aroclor mixtures with a keen eye on specific dechlorination patterns (ortho versus meta and para).
- We will continue to modify aerobic biodegradation conditions such that biodegraded products can be evaluated in vitro using LPS stimulation as an index.
- We will determine whether known intermediates in the biodegradation of PCBs can influence LPS induced B cell proliferation. These will include both hydroxy biphenyls and chlorobenzoates. Our preliminary data suggests these compounds are not immunotoxic although aerobic biodegraded aroclor mixtures may be immunotoxic (not shown).
Journal Articles on this Report : 1 Displayed | Download in RIS Format
Other project views: | All 14 publications | 3 publications in selected types | All 2 journal articles |
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Type | Citation | ||
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Stack A, Altman-Hamamdzic S, Morris PJ, London L. Polychlorinated biphenyl mixtures (Aroclors) inhibit LPS-induced murine splenocyte proliferation in vitro. Toxicology, Volume 139, Issue 1-2, November 29, 1999, Pages 137-154. |
R826687 (2000) R826687 (Final) |
not available |
Supplemental Keywords:
PCBs, soils and sediments, health effects, bioremediation, southeast., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Waste, Environmental Chemistry, Health Risk Assessment, chemical mixtures, Risk Assessments, Analytical Chemistry, Biochemistry, Physical Processes, Bioremediation, ecological risk assessment, complex mixtures, detoxification, aerobic degradation, biodegradation, PCBs, exposure, environmental mutagens, PCB, in situ bioremediation, human exposure, bioacummulation, aroclor, immune systems, bioaccumulation, human health risk, immune responseProgress 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.