Grantee Research Project Results
Impacts of Hg, PCB, and HCH Contaminants on Human and Fish Immune Cells
EPA Grant Number: U915216Title: Impacts of Hg, PCB, and HCH Contaminants on Human and Fish Immune Cells
Investigators: Sweet, Leonard I.
Institution: University of Michigan
EPA Project Officer: Lee, Sonja
Project Period: January 1, 1997 through January 1, 2000
Project Amount: $102,000
RFA: STAR Graduate Fellowships (1997) RFA Text | Recipients Lists
Research Category: Fellowship - Toxicology , Academic Fellowships , Human Health
Objective:
The objectives of this research project were
to: (1) characterize the mechanisms of immunomodulation by mercury ([HCH]
as HgCl2), polychlorinated
biphenyls ([PCBs], as Aroclor 1254), and hexachlorocyclohexane (-,
-, (
-, and
-HCH isomers) environmental chemical contaminants; (2) develop
protocols
for testing and hazard assessment of uncharacterized chemical stressors;
and (3) analyze for levels of Hg, PCBs, and HCHs in fish and human immune
system
tissue.
Approach:
This research project determined the effects of the Hg, PCBs, and HCHs with in vitro assays on human (neutrophil) and on lake trout (thymocyte) primary immune system cells. Multiparameter flow cytometry and fluorescence spectroscopic methods were employed to assess chemically induced effects on cell communication (i.e., apoptosis signals via phospholipid structure), function (i.e., chemotaxis via cytoskeletal changes, and thiol homeostasis), and survival (via protease activation, and morphology). The fish and human immune system cells showed similar sensitivity to the chemicals for the immunological endpoints, with effective concentrations of 0.3 µM for mercury, 0.75 µg/mL for Aroclor 1254, and 10 µM for HCH isomers. In general, chemical-induced changes in the cytoskeleton proved to be a more sensitive endpoint as compared to apoptosis and thiol alteration. Results from the in vitro assays also were compared to total Hg and PCB (as sum of 80 congeners) residue concentrations detected in lake trout tissue (whole fish, kidney, spleen) that were collected from Six Fathom Bank and Saginaw Bay Lake Huron (n = 60 fish), in laboratory-reared lake trout, as well as in human and fish blood donors. The PCB concentrations in whole-fish tissue (range 1-4.4 mg/kg), spleen (58-293 µg/kg), and kidney (34-95 µg/kg) were generally higher in Saginaw Bay samples, and the levels were highly correlated with mean length, weight, and age. Mercury concentrations in fish tissue did not exceed the threshold for the Michigan health advisory at 0.5 mg/kg.
Supplemental Keywords:
fellowship, immunomodulation, mercury, polychlorinated biphenyls, PCBs, Aroclor 1254, Hg, hexachlorocyclohexane, HCH, fish immune cells, trout, Lake Huron., Health, Scientific Discipline, Toxicology, Health Risk Assessment, Risk Assessments, biological pathways, mercury, environmental risks, animal model, human exposure, PCB, immunotoxicology, HCH, human health risk
Progress 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.