LACK OF SUPPRESSIVE EFFECTS OF MIXTURES CONTAINING LOW-LEVELS OF METHYLMERCURY (MEHG), POLYCHLORINATED DIBENZO-P-DIOXINS (PCDDS), POLYCHLORINATED DIBENZOFURANS (PCDFS), AND AROCLOR BIPHENYLS (PCBS) ON MIXED LYMPHOCYTE-REACTION, PHAGOCYTIC, AND NATURAL-KILLER-CELL ACTIVITIES OF RAT LEUKOCYTES IN-VITRO

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to dete rmine the immunotoxicity of mixtures containing low levels of methylme rcury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinat ed dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs) . The mixtures were based on the concentrations of the chemicals in fi sh flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1- 2 mu g/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-te trachlorodibenzo-p-dioxin, 1,2,3,7,8-penta-chlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrac hlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclo r PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 mu g/ml), or c ombinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immun ological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cu ltured with mitomycin C-treated Long-Evans splenocytes by [H-3]thymidi ne uptake. Exposure to MeHg (2 mu g/ml) alone or with PCB/PCDD/PCDF re sulted in significant cytolethality in rat splenocytes, peritoneal leu kocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixture s, PCDD/PCDF mixtures, 0.1 mu g Me/Hg/ml (noncytolethal), or PCB/PCDD/ PCDF mixtures with 0.1 mu g MeHg/ml caused no suppression of splenocyt e MLR response, splenic NK cell-mediated lysis of Yac-1 cells, or phag ocytosis of fluorescent beads by splenic , peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects o n the immune functions assayed, and thus produced no additive immunoto xicity. However, in order to predict the potential risk of these chemi cal mixtures to the human immune system, in vivo animal studies with b lood (tissue) levels compatible with the levels of MeHg, PCBs, and PCD Ds/PCDFs in exposed human populations should be evaluate.