Fig. 5

Central metabolic activity of arsenite-transformed BAsT cells is sensitive to the tumor microenvironment. Human bronchial alveolar BEAS2B cells were transformed by exposure to 1 µM Na₂AsO₃ for 18 weeks before subcutaneous xenograft of the transformed cells (BAsT cells) into NSG mice. After 4 months, mice were fed the ¹³C₆-Glc enriched liquid diet for 18 h (cf. Fig. 1) before necropsy. Tumor tissues were processed and analyzed by IC-UHR-FTMS as described in Fig. 3. A ¹³C₆-Glc tracer experiment was also performed for the BAsT cells as in vitro culture for 24 h in DMEM before extraction for polar metabolites, followed by IC-UHR-FTMS analysis (n = 3). Shown in a–c, d–k, and l are the fractional enrichments in the isotopologues of metabolites derived from glycolysis, the Krebs cycle, and the PPP, respectively. F1,6BP: fructose-1,6-bisphosphate; S7P: sedoheptulose-7-phosphate; BAsT-C (black square): in vitro cell cultures; BAsT-T (red square): tumor xenografts; all other abbreviations are as in Fig. 3. The x-axis represents the number of ¹³C atoms present in each compound. Values shown were mean ± SEM (n = 3). ^* 0.01 < P < 0.05; ^** 0.001 < P < 0.01; ^*** P < 0.001, two-tailed t-test (see Methods)