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Serum supplementation modulates the effects of dibutyltin on human natural killer cell function
Citation:
Whalen, M. M., J. DEWITT, AND R. W. LUEBKE. Serum supplementation modulates the effects of dibutyltin on human natural killer cell function. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 104(2):312-319, (2008).
Impact/Purpose:
Humans may be exposed to DBT (and other organotins) used as stabilizers in PVC water pipe via leaching into drinking water or by consuming foods that have accumulated DBT from a contaminated environment. Published data generated in vitro under serum-free conditions suggested that lysis of tumor cells by human NK cells may be compromised in individuals at the upper range of reported dibutyltin (DBT) serum concentrations. However, because DBT binds to serum components, I was concerned that the published in vitro dose response data may not accurately reflect the in vivo immunotoxic dose response, or the actual intracellular dose delivered to NK cells.
Description:
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 destruction of target cells by NK cells exposed to DBT in serum-free cell culture medium. However, because serum is a component of human exposure (approximately 50-60%), we investigated whether, and to what extent, the accumulation of DBT (exposure levels of 1-10 μM) in freshly isolated NK cells was affected by various serum concentrations. Ten percent serum affected neither the accumulation of DBT in NK cells nor NK cell lytic activity appreciably compared to serum-free conditions after 1h of exposure. Fifty percent serum supplementation resulted in an approximately 20% decrease in the accumulation of DBT compared to serum-free medium after a 1h exposure at the 10 μM concentration. Additionally, 50% serum attenuated suppression of NK cell lytic activity by 2.5 and 5 μM DBT after a 1h exposure. The results of these studies indicate that serum concentration in the exposure medium influences the level of DBT that is accumulated by NK cells, and modulates the effect of DBT on NK cell function. These data are important in interpreting the immunotoxic effects of in vitro DBT exposures reported in previous studies and utilizing such information in risk assessment.
URLs/Downloads:
Serum supplementation modulates the effects of dibutyltin on human natural killer cell function