title: Serum supplementation modulates the effects of dibutyltin on human natural killer cell function.
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 200 microM and nearly complete loss of lytic function was observed at DBTi above 300 microM for one h. However, an intracellular concentration of 50 microM 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.
authors.affiliation: Department of Chemistry, Tennessee State University, Nashville, Tennessee 37209, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Whalen
authors.forename: Jamie C
authors.initials: JC
authors.lastname: DeWitt
authors.forename: Robert W
authors.initials: RW
authors.lastname: Luebke
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D009947:Organotin Compounds / Q000378:metabolism / Q000633:toxicity*; D044967:Serum / Q000276:immunology*
chemical_list: D004785:Environmental Pollutants; D009947:Organotin Compounds; C056189:di-n-butyltin