The structure-dependent induction of aryl
hydrocarbon hydroxylase (AHH) and
ethoxyresorufin O-deethylase by
2,3,7,8-tetrachlorodibenzo-p-dioxin,
2,3,7,8-tetrachlorodibenzofuran, and 1,2,4,7,8-pentachlorodibenzo-p-dioxin was determined in the MCF-7, T47-D, and MDA-MB-231 human
breast cancer cell lines. Both the MCF-7 and T47-D cells were responsive to the induction effects of the halogenated aryl
hydrocarbons and the structure-induction relationships were comparable to the reported structure-activity (induction, receptor binding, and toxicity) relationships observed in rodents and rodent cells in culture. The induction of
ethoxyresorufin O-deethylase in the T47-D cells was the most sensitive aryl
hydrocarbon (
Ah) receptor-mediated response in both cell lines and this
enzyme activity was more inducible than aryl
hydrocarbon hydroxylase. In contrast, the three congeners were inactive as
monooxygenase enzyme inducers in the MDA-MB-231 cells. Despite the differential Ah responsiveness of the cell lines, incubation of the cells with [3H]-2,3,7,8-
tetrachlorodibenzo-p-dioxin followed by extraction of the nuclei with high
salt and velocity sedimentation analysis of the extracts showed that specifically bound nuclear
Ah receptor complexes were present in the three cell lines. The sedimentation coefficients (and levels) for the
nuclear receptors were 6.6 S (32.1 fmol/mg
protein/mg
DNA), 6.9 S (61.6 fmol/mg
protein/mg
DNA), and 7.4 S (38.2 fmol/mg
protein/mg
DNA) in the T47-D, MCF-7, and MDA-MB-231 cell lines, respectively. Cytosolic receptor was also detected in the MCF-7 and MDA-MB-231 cells. Thus, despite the differences in Ah responsiveness of the T47-D and MDA-MB-231 cells, comparable levels of
nuclear receptor were detected in both cell lines. Furthermore, the elution profiles of the
nuclear receptors from
DNA-
Sepharose columns by using a
salt gradient were similar and this suggested that defects in the
DNA-binding activity of MDA-MB-231
nuclear receptor complexes were not major factors associated with their failure to respond to
2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.