Fig. 2.

Effect of drug treatment and induction of cellular necrosis on ¹³C label flux between [1,4-¹³C₂]fumarate and [1,4-¹³C₂]malate in EL-4 lymphoma cell suspensions. (A) Ratio of the average [1-¹³C] and [4-¹³C]malate peak intensity/total hyperpolarized ¹³C signal intensity (± SD, n = 3). It has been corrected for total cell number, which includes viable, apoptotic, and necrotic cell populations. Untreated cells (circles), cells 16 h after etoposide treatment (triangles), and lysed cells (squares). The open symbols refer to experiments performed with 10 mM hyperpolarized [1,4-¹³C₂]fumarate only, and the filled symbols show experiments performed with the coadministration of 50 mM nonhyperpolarized and unlabeled succinate; for clarity, the open symbols have been offset by −0.5 s and the filled symbols have been offset by +0.5 s. (B) Rate of malate production (calculated from the initial slope of malate amplitude/total ¹³C signal over time) plotted against the percentage of cell necrosis in each experiment. The conditions used to vary the levels of necrosis are described in Materials and Methods.