ToxSci Advance Access published online on April 25, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn082
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Serum supplementation modulates the effects of dibutyltin on human natural killer cell function
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* Department of Chemistry, Tennessee State University, 3500 John A. Merritt Blvd. Nashville, TN 37209, mwhalen{at}tnstate.edu
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599; Immunotoxicology Branch, Experimental Toxicology Division, NHEERL, U. S. Environmental Protection Agency, Research Triangle Park, NC, 27709, dewitt. jamie{at}epa.gov
Immunotoxicology Branch, Immunotoxicology Branch, Experimental Toxicology Division, NHEERL, U. S. Environmental Protection Agency, Research Triangle Park, NC 27709, luebke.robert{at}epa.gov
Correspondence: Robert W. Luebke, Ph.D. US EPA MD B143-01 109 T.W. Alexander Drive Research Triangle Park, NC 27709 Phone: 919.541.3672 Fax: 919.541.3538 Email: Luebke.robert{at}epa.gov
Received December 30, 2007; revision received April 11, 2008; accepted April 20, 2008
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Abstract |
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NK cells are a subset of lymphocytes capable of killing tumor cells, virally infected cells and antibody coated cells. Dibutyltin dichloride (DBT) is an organotin used as a stabilizer in polyvinyl chloride (PVC) plastics and as a deworming product in poultry. DBT may leach from PVC water supply pipes and therefore poses a potential risk to human health. We previously reported diminished NK cells lysis of tumor cells following exposure to DBT in serum-free cell culture medium. However, under in vivo conditions, circulating cells will be exposed to DBT in the presence of 100% plasma; thus we investigated whether serum supplementation and incubation time modulates DBT effects on NK cell killing and the accumulation of DBT in freshly isolated NK cells, to determine whether a serum-free model accurately predicts possible effects of DBT on human NK cells under in vivo conditions. Lytic function was decreased by approximately 35% at an intracellular DBT concentration (DBTi) of 200 µM and nearly complete loss of lytic function was observed at DBTi above 300 µM for one h. However, an intracellular concentration of 50 µM DBT, achieved over 24 h of exposure in 50% serum, reduced lytic function by 50%. Thus, conditions that reflect prolonged contact with circulating DBT, in the presence of serum, suggest that NK cell activity is decreased at lower DBTi. These data indicate that the model is useful in predicting potential human effects of relatively low intracellular DBT concentrations.
Key Words: dibutyltin dichloride; natural killer cells; immunotoxicity; in vitro methods.