ALTERATIONS IN SPLENOCYTE PROTEIN-KINASE-C (PKC) ACTIVITY BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN-VIVO

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on growth fa ctor-coupled activation of nuclear protein kinase C (nPKC) and on the subcellular distribution of PKC activity in rat splenocytes were inves tigated. Seven days after a single injection of TCDD (50 mu g/kg body weight), cytosolic and particulate PKC activity was significantly high er in splenocytes from TCDD-treated rats or pair-fed control rats comp ared to ad libitum-fed animals. In a separate experiment, purified spl enocyte nuclei from TCDD-treated animals and controls were used to stu dy activation of nPKC by growth factors and other trophic agents. Grow th factor-stimulated nPKC activation was attenuated in splenic nuclei from TCDD-treated rats compared to vehicle-treated controls. Evidence presented here suggests that the cellular mechanism of TCDD toxicity l eading to immunosuppression in rodents may be mediated in part by unco upling of growth factor receptors linked to PKC activation at the leve l of the nucleus. However, changes in total splenocyte PKC activity ap pear to be correlated with hypophagia since cytosolic and particulate PKC levels were elevated in TCDD-treated rats and their pair-fed partn ers.