Effects of in vitro exposure to low levels of organotin and carbamate pesticides on human natural killer cell cytotoxic function

Abstract

Human natural killer (NK) lymphocytes play a central role in immune system defense against viral infection and against the formation of primary tumors. Organotin (OT) pesticides have been used in industrial and agricultural applications, and OT contamination has been reported in water, sediment, and fish. Carbamate pesticides are currently used in agricultural chemicals. Two specific carbamates used in agriculture are ziram and maneb; ziram also is used as an additive in rubber products including latex gloves. In previous studies we demonstrated that at concentrations in the 150-200 nM range, the OTs tributyltin (TBT) and triphenyltin (TPT) were capable of disrupting the function of human NK cells after incubations to as short as 24 h. Previously, we also examined the effects of ziram and maneb at higher concentrations on the cytotoxic function of human NK cells. The current study examined the effects of exposure of up to 6 days to lower concentrations of each of these compounds on the cytotoxic function of NK cells. The OTs were studied at concentrations ranging from 200 to 10 nM; ziram was studied at concentrations of 2.5 microM-125 nM and maneb at concentrations of 10-1 microM. These conditions were studied both in highly purified NK cells and in a mixture of lymphocytes containing both T and NK cells. As little as 25 nM TBT decreased the function of purified NK cells after 24 and 48 h, whereas 10 nM TBT was effective after 6 days. The lowest level of TPT that was effective at 24 h was 50 nM whereas the results after 48 h and 6 days were similar to those seen with TBT. The presence of T lymphocytes diminished the effects of both TBT and TPT on NK cytotoxic function. A concentration of ziram as low as 125 nM produced significant loss of cytotoxic function in highly purified NK cells (65% decrease in function after 6 days). The toxicity of each of the compounds studied increased very significantly with length of exposure.