Document 1g5pkdXBjd1LM2Bddv7qDK5ro

*i\a EFFECTS.OF. 2,3,7,8:TETRACHLORODJBENZO-p-DJOXJN ' (TCDD) ON SPLENic' LYMPHOCYTE TRANSFORMATION IN MICE AFTER SINGLE AND REPEATED EXPOSURES R. P. Sharma Toxicology Program Utah State University Logan, Utah 84322 P. J. Gehring Toxicology Research Laboratory The Dow Chetnical Co. * Midland, Michigan 4S640 i- *" f 2.3,7,8-Tetrachlorodibenzo-/?-dioxin (TCDD) is one of the most toxic mzn-rmdc chemicals.1 Manifestations of its toxicity arc diffuse and include atrophy of the thymus. It had been reported to be an immunosuppressant. Buu-Hoi et al.1 reported that TCDD produced a dose-related atrophy of the thymus at sublethal dose* levels. More intense investigations revealed that TCDD depressed the delayed type tubercu lin skin reactivity in young guinea pics but not in rats.-5The graft-versus-host (GVH) reactivity of mice spleen cells was also reduced.3 In a follow-up report. Vos and Moore* showed the suppression of cellular immunity in rats and mice after maternal and postnatal exposures to TCDD. Allograft (tail skin) rejection limes were also prolonged in both rats and mice. The response of rat thymocytes and spleen cells to phytohcmagalutinin (PHA) was reduced by TCDD exposure. No effect was noticed on the response of thymocytes ip concanavatin A (Con A). Young animals were much more sensitive to the immuno suppressive effects of TCDD. Thigpen et al/ have reported that sublethal levels of TCDD increased mortality and shortened the incubation lime in mice when challenged by Salmonella infection. On the other hand, there was no effect on the mortality of mice infected with pseudorabics virus (PRV). The above findings suggest a possible selective depression of immune processes by TCDD. The cellular processes appear to be more sensitive than the humoral ones. In addition, there appears to be a species and agc-dcpcndcnt v-ariatton in the immuno logic effects of TCDD. The effects of varying levels of TCDD on mice were hence investigated on the immune processes. In addition, the effects of a single exposure to TCDD were evaluated at different time intervals. Splenic lymphocytes from treated animals were cultured in vitro with and w-ithout the presence of mitogenic lectins that stimulate different populations of these cells and the incorporation of labeled thymidine was measured to evaluate the blast formation. METHODS Male CD-I mice (weighing approximately 2S g each at the beginning of the experiment) were obtained from Charles River (Willmingion, Mass.) and divided into five groups after an initial one week of acclimation. These animals "ere housed two 87 0 0 7 7 -r? :3 /7 9 /0 )2 0 -0 * i: S 0 l.:i/0 c 1979. NYa S