BENZO[A]PYRENE-RESISTANT MCF-7 HUMAN BREAST-CANCER CELLS - A UNIQUE ARYL HYDROCARBON-NONRESPONSIVE CLONE

Wild-type MCF-7 human breast cancer cells were cultured for 3 months i n 1 mu M benzo[a]pyrene (BaP), and resistant clones were screened for inducibility of CYP1A1 gene expression by 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD). One of the BaP-resistant (BaPR) clones exhibited uniqu e genotypic expression which distinguished it from both wild type and drug-resistant (Adr(R)) variant MCF-7 cells. Glutathione levels, gluta thione S-transferase activities, estrogen receptor levels, estrogen re sponsiveness, and expression of the multidrug-resistant MDR1 and MRP m RNA levels were similar in the wild-type and BaPR cells, whereas these parameters were reported to be altered in Adr(R) cells. In contrast, TCDD induced CYP1A1 gene expression and inhibited selected estrogen-in duced responses in wild-type but not BaPR MCF-7 cells. Treatment of wi ld-type and BaPR cells with [H-3]TCDD resulted in formation of the rad io-labeled aryl hydrocarbon (Ah) 6 S nuclear receptor complex in both cell lines, The loss of Ah responsiveness in the BaPR variant cells co rrelated with the failure of the nuclear or transformed cytosolic Ah r eceptor complex to bind genomic dioxin-responsive elements as determin ed in gel retardation assays.