ToxSci Advance Access originally published online on April 25, 2008
Toxicological Sciences 2008 104(2):312-319; doi:10.1093/toxsci/kfn082
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Serum Supplementation Modulates the Effects of Dibutyltin on Human Natural Killer Cell Function
,
,1
* Department of Chemistry, Tennessee State University, Nashville, Tennessee 37209
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Immunotoxicology Branch, Immunotoxicology Branch, Expaerimental Toxicology Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709
1 To whom correspondence should be addressed at US EPA, MD B143-01, 109 T.W. Alexander Drive, Research Triangle Park, NC 27709. Fax: (919) 541-3538. E-mail: Luebke.robert{at}epa.gov.
Received December 30, 2007; accepted April 20, 2008
 |
Abstract |
|---|
Natural killer (NK) cells are a subset of lymphocytes capable of killing tumor cells, virally infected cells and antibody-coated cells. Dibutyltin (DBT) dichloride is an organotin used as a stabilizer in polyvinylchloride (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 (DBTi) concentration of 200µM and nearly complete loss of lytic function was observed at DBTi above 300µM for one h. However, an intracellular concentration of 50µM 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 DBTi concentrations.
Key Words: dibutyltin dichloride; natural killer cells; immunotoxicity; in vitro methods.
Disclaimer: This report has been reviewed by the Environmental Protection Agency's Office of Research and Development, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.