EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ON 17-BETA-ESTRADIOL-INDUCED GLUCOSE-METABOLISM IN MCF-7 HUMAN BREAST-CANCER CELLS - C-13 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY STUDIES

The effects of 17-beta-estradiol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their combination on the metabolism of [1-C-13] glucose we re determined in cell suspensions of wild-type MCF-7 human breast canc er cells, by C-13 NMR spectroscopy. Preliminary studies showed that, d uring the 7-hr duration of the NMR experiment, the cells maintained th eir viability and their aryl hydrocarbon responsiveness. Lactate was t he major glucose metabolite detected in these studies, and the rate of lactate formation in the untreated (control) and 17-beta-estradiol (1 0(-9) M)-treated cells was 60 and 86 fmol/cell/hr, respectively; this represented a 40% increase in lactate formation in the cells treated w ith 17-beta-estradiol; comparable results were observed for the percen tage of glucose converted into lactate. In contrast, TCDD (10(-9) M) d id not significantly alter the rate of glucose metabolism or lactate f ormation. Co-treatment of the cells with 17-beta-estradiol (10(-9) M) plus TCDD (10(-8) to 10(-10) M) showed that TCDD completely inhibited the 17-beta-estradiol-induced metabolism of [C-13] glucose to lactate in MCF-7 cells. In contrast, 2,8-dichlorodibenzo-p-dioxin (10(-8) M), a weak aryl hydrocarbon receptor agonist, did not inhibit estrogen-ind uced glucose-to-lactate metabolism in MCF-7 cells. In addition, it was shown that TCDD caused a significant decrease in 17-beta-estradiol-in duced lactate formation within 1 hr after treatment, whereas the induc tion of monooxygenase activity was not observed until 3 hr after expos ure of the cells to TCDD. These data indicate that TCDD-induced 17-bet a-estradiol metabolism is not related to the decrease in the rate of c onversion of glucose to lactate. These results further define the anti estrogenic responses elicited by TCDD and show that C-13 NMR spectrosc opy provides a unique method for measuring, in real time, the effects of TCDD on specific metabolic pathways.