Extended Data Fig. 7: Dynamic metabolic response to radiation therapy in GBM and cortex.
From: Rewiring of cortical glucose metabolism fuels human brain cancer growth
a, Fluxes through purine synthesis after RT estimated by analysing orthotopic tumour and cortex tissues from GBM38-bearing mice that were treated with whole cranial RT (8 Gy), immediately (<5 min post-RT) infused with [U13C]glucose and serially euthanized at varying timepoints following treatment. b-r, Flux values for the following reactions were approximated using time-course enrichment as described in Supplementary Methods: de novo IMP synthesis (b), conversion of IMP to GMP (c), conversion of IMP to AMP (d), conversion of PRPP + hypoxanthine to IMP (e), conversion of PRPP + guanine to GMP (f), conversion of R1P + guanine to guanosine (g), conversion of adenosine to AMP (h), conversion of GMP to GDP (i), GDP exit from model boundary (j), conversion of GMP to guanosine (k), conversion of guanosine + R1P to guanine (l), AMP exit from model boundary (m), conversion of R1P + hypoxanthine to inosine (n), conversion of IMP to inosine (o), conversion of inosine to R1P + hypoxanthine (p), conversion of adenosine to inosine (q), and conversion of AMP to IMP (r). Solid lines indicate estimated fluxes, and shaded regions indicate 95% confidence intervals. Fluxes were approximated using 3–9 samples per timepoint with samples originating from 1–3 mice per group and 3 samples per mouse. s, Levels of m + 4 IMP in orthotopic GBM38 tumours harvested from control or cranial RT (8 Gy)-treated mice infused with 15N4-inosine. Data are mean ± s.d. of tumour samples from 4–5 mice per group containing 1–2 tumour foci each. t-v, Relative levels of de novo m + 3 GMP (t), de novo m + 2 IMP or (u) de novo m + 2 AMP (v) in orthotopic GBM38 tumours harvested from control or cranial RT (8 Gy)-treated mice infused with 15N-glutamine. Data are mean ± s.d. of tumour samples isolated from 3 mice per group containing 1–3 intracranial tumour foci each. In s-v, groups were compared by t-test. Abbreviations: PRPP (phosphoribosyl pyrophosphate), R1P (ribose 1-phosphate).
