Stable isotope resolved metabolomics of lung cancer in a SCID mouse model.

We have determined the time course of [U-C]-glucose utilization and transformations in SCID mice via bolus injection of the tracer in the tail vein. Incorporation of C into metabolites extracted from mouse blood plasma and several tissues (lung, heart, brain, liver, kidney, and skeletal muscle) were profiled by NMR and GC-MS, which helped ascertain optimal sampling times for different target tissues. We found that the time for overall optimal C incorporation into tissue was 15-20 min but with substantial differences in C labeling patterns of various organs that reflected their specific metabolism. Using this stable isotope resolved metabolomics (SIRM) approach, we have compared the C metabolite profile of the lungs in the same mouse with or without an orthotopic lung tumor xenograft established from human PC14PE6 lung adenocarcinoma cells. The C metabolite profile shows considerable differences in [U-C]-glucose transformations between the two lung tissues, demonstrating the feasibility of applying SIRM to investigate metabolic networks of human cancer xenograft in the mouse model. [ABSTRACT FROM AUTHOR]