2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN INDUCED ALTERATIONS IN PROTEIN-PHOSPHORYLATION IN GUINEA-PIG ADIPOSE-TISSUE

An in situ (explant tissue culture) model has been developed to study the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hormones, an d growth factors either alone or in combination. In our model system, the effect of TCDD on protein phosphorylation was greatly affected by the presence or the absence of externally added D-glucose. In the pres ence of a physiologically relevant level of glucose (13.3 mM), TCDD cl early stimulated protein phosphorylation as in the case of in vivo dat a. However, in the absence of D-glucose, TCDD clearly inhibited protei n phosphorylation. On the other hand, TCDD reduced the glucose uptake activity in isolated adipose tissue either in the presence or absence of D-glucose (13.3 mM). Therefore, the TCDD-induced reduction of gluco se transport does not appear to be related directly to the simultaneou s rise in protein phosphorylation. For comparison, several agents whic h are known to affect protein phosphorylation were tested. These hormo nal agents generally affected the TCDD-untreated adipose tissues in th e manner expected from their known actions, indicating that this in si tu model is an adequate system to study their independent actions. The TCDD-treated adipose tissue samples showed only mild or insignificant response to these hormonal stimuli. In terms of the changes in the pa ttern of protein phosphorylation activities, the action of TCDD appear ed to resemble that of EGF and T3. Since under in situ conditions no a gents such as EGF or T3 can be expected to be present, the observed TC DD-induced changes are suggestive of the basic intracellular changes i n cellular activities. The types of TCDD-induced protein kinases appea r to be protein tyrosine kinases and protein kinase C.