Effect of the tumor promoters 2,3,7,8-tetrachlorodibenzo-p-dioxin -TCDD- and 3,3',4,4'tetrachlorobiphenyl -TCB- on leukemia cell differentiation

Tumor promoters are known to interfere with cellular differentiation. For instance, the tumor promoting phorbol esters inhibit erythroid differentiation and stimulate monocyte differentiation in various leukemia cell lines. To elucidate the mechanisms of tumor promotion by TCDD and TCB, we studied their effects on differentiation in two erythroleukemia cell lines, i.e., the human K562 cells and the murine Friend cell line F4-6. TCDD (10high-12M) and TCB (10high-7M) partially (30%) inhibited the hemin-induced differentiation of K562 cells. In contrast, both agents stimulated the DMSO-induced differentiation (2 to 3 fold), but not the hemin- or butyrate-induced differentiation of F4-6 cells. These results suggest that leukemia cells are a very sensitive model to study the effect of tumor promoting polychlorinated dioxins and biphenyls on cellular differentiation. Supported by grants from Deutsche Forschungsgemeinschaft.