IMMUNOTOXICITY OF ENVIRONMENTALLY RELEVANT MIXTURES OF POLYCHLORINATED AROMATIC-HYDROCARBONS WITH METHYL MERCURY ON RAT LYMPHOCYTES IN-VITRO

The immunosuppressive effects of methyl mercury (MHg), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and dibe nzofurans (PCDFs) are well established at high exposure levels but unc lear at low exposure levels. We exposed Fischer 344 rat splenocytes, t hymocytes, and peripheral blood lymphocytes in vitro for 72 h to MHg ( 0.1, 2 mu g/ml), PCDD/PCDF mixtures (1, 15 pg/ml) of three PCDDs (2,3, 7,8-tetrachlorodibenzo-p-dioxin, 1, 2,3,7,8-pentachlorodibento-p-dioxi n, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8- tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor(R) (1242, 1254, 1260), PCB mixtures (0.01, 0.5 mu g/ml), or co mbinations of MHg/PCB/PCDD/PCDF mixtures Mitogenic responses of lympho cytes to concanavalin A, phytohemagglutinin, or lipopolysaccharide/dex tran sulfate were determined by H-3-thymidine uptake: cytotoxicity and intracellular Ca2+ were determined by flow cytometry. Methylmercury ( 2 mu g/ml and PCB/ PCDD/PCDF mixtures with 2 mu g/ml MHg decreased the viability of splenocytes to 57 and 40% at 4 and 24 h, respectively. B asal intracellular calcium ion levels were unaffected by the treatment s. Methylmercury suppressed the responses of lymphocytes to T and B ce ll mitogens. All combinations of MHg/PCB/PCDD/PCDF mixtures decreased mitogenic responses to levels similar to those to MHg alone. In contra st, PCB and PCDD/PCDF mixtures did not suppress but augmented response s of splenocytes and peripheral blood lymphocytes to T cell mitogens. Overall, no interactive toxicity was observed with MHg/PCB/PCDD/PCDF m ixtures on cytotoxicity and lymphocyte mitogenic responses. Therefore, MHg may pose a greater threat than organochlorines to the mammalian I mmune system.