Immunomodulation of human natural killer cell cytotoxic function by triazine and carbamate pesticides

Triazine (atrazine) and carbamates (maneb, metiram, and ziram) are used as pesticides on a variety of crops around the world. To our knowledge, there have been no studies dealing with the effects of these compounds on human natural killer (NK) cells cytotoxic function. NK cells play a central role in immune defense against tumor development and viral infections. Thus, any agent that interferes with the ability of NK cells to lyse their targets could increase the risk of tumor incidence and/or viral infections. In this study, we examined the effects of atrazine, maneb, metiram, zineb, and ziram on the ability of human NK cells to lyse tumor cells. The compounds were tested in both purified NK cells as well as a cell preparation that contained both T and NK lymphocytes (T/NK cells). Lymphocytes were exposed to the compounds for periods of time ranging from I h to 6 days. Exposure of highly purified NK cells to 10 muM atrazine, maneb, or metiram inhibited K562 tumor cell lysis by 63 +/- 25, 95 +/- 4, and 50 +/- 6%, respectively, after a 24 h exposure and by 83 +/- 21, 70 +/- 39, and 48 +/- 41% after a 6-day exposure. Exposure to 2.5 muM ziram for 24 h caused a 99 +/- 2% decrease in lytic function and at I muM for 6 days caused a 96 +/- 4% decrease. However, when T/NK cells were exposed to atrazine. maneb, or metiram for 24 It only 10 muM atrazine and munch, caused a significant decreases in lytic function (61 +/- 13 and 38 +/- 18%) and after 6 days only atrazine was inhibitory (54 +/- 12%). A 24-h exposure to 2.5-muM ziram caused a 41 +/- 51% decrease in function, but a 6-day exposure to I muM ziram caused no inhibition of lytic function. The results provide evidence of relative toxic potential for the five compounds and the immunomodulatory effects on both T and NK lymphocyte function. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.