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EFFECTS OF 2,3,7,8‐TETRACHLORODIBENZO‐p‐DIOXIN (TCDD) ON SPLENIC LYMPHOCYTE TRANSFORMATION IN MICE AFTER SINGLE AND REPEATED EXPOSURES

Male CD-1 mice were orally treated with 0.01, 0.1, 1 and 10 micrograms TCDD/kg body wt./week for up to 8 weeks. Randomly selected animals were sacrificed at 2, 4, and 8 weeks of exposure. An additional group was given orally 10 micrograms TCDD/kg and the animals similarly sacrificed. Splenic lymphocytes from these animals were cultured in vitro with or without the presence of phytomitogens, phytohemagglutinin, and pokeweed mitogen. The incorporation of 3H-thymidine was measured as an indication of relative blast formation. Exposure of animals to TCDD, even at the lowest level (0.01 microgram/kg/wk for 2 weeks) caused a marked increase in the thymidine uptake by cultured lymphocytes. The blastogenic response of mitogens was reduced at high levels of TCDD exposure, indicating an immunosuppressive effect. Following a single treatment with 10 micrograms TCDD/kg, the increase in the blast formation was noted at 2 weeks, the effect reduced at 4 weeks, and no difference noticed in treated vs. control cultures 8 weeks after the treatment. Small doses of TCDD stimulate the splenic lymphocyte transformation and this effect, although somewhat dose-related, can be reversed in a relatively short period of time.