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(643) Immunomodulatory effects of in vitro exposure to organochlorine mixtures in marine mammals and mice.
Levin, Milton*,1, Mori, Chiharu1, De Guise, Sylvain1, 1 University of Connecticut, Storrs, CT, USA
ABSTRACT- The immunomodulatory effects of PCBs on marine mammals have been suspected, yet rarely measured. Contaminant induced immunosuppression has been suspected as a co-factor in the deaths of thousands of cetaceans and pinnipeds. The effects of individual PCB congeners have been previously studied in laboratory animals, but little has been done on the effects of mixtures of organochlorine compounds. The present study is aimed at characterizing immunomodulatory potential for mixtures of organochlorines compared to that of individual compounds, and compares the relative sensitivity of different species of marine mammals and mice. Immune assays evaluated included: (i) lymphocyte proliferation, the ability of lymphocytes to divide upon stimulation with a mitogen; and (ii) phagocytosis, the ability of phagocytic cells to engulf fluorescent microspheres. Four PCB congeners, PCB 138, PCB 153, PCB 169, and PCB 180, as well and 2,3,7,8-TCDD were tested. Using mitogen-induced lymphocyte proliferation with the T-cell mitogen, ConA, immunomodulatory effects were demonstrated upon exposure to more mixtures in harbors seals (19) than belugas (12), mice (6), and Northern fur seals (4). Mouse cells showed effects for only four of the 20 mixtures that affected lymphocyte proliferation in marine mammals. Using the B-cell mitogen, LPS, Northern fur seal lymphocyte proliferation was affected by two mixtures, whereas no effects were seen using beluga and mouse cells. Beluga monocyte phagocytosis was decreased by two mixtures while four mixtures increased Northern fur seal neutrophil phagocytosis. Our results suggest that the widely used mouse model may not accurately represent the risks associated with exposure to mixtures of organochlorines in all species. Our results suggest both synergistic and antagonistic interactions between congeners. Testing the relative sensitivity to immunomodulatory effects of contaminants and contaminant mixtures between different species of marine mammals will have important implications for risk assessment as well as conservation and management strategies.
Key words: immunotoxicity, organochlorine, marine mammal, mice
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