COMPARATIVE NMR-STUDY OF A DIFFERENTIATED RAT HEPATOMA AND ITS DEDIFFERENTIATED SUBCLONE CULTURED AS SPHEROIDS AND AS IMPLANTED TUMORS

H4IIEC3 (H4), a differentiated rat hepatoma line and H5, its dediffere ntiated subclone, were investigated as proliferating spheroids and as implanted subcutaneous tumors in juvenile rats. H4 cells formed tight, round spheroids whereas H5 cells formed loose, grape-like structures. P-31 MR spectra showed that phosphocreatine was present in H5 spheroi ds but not in H4 spheroids or tumors. [C-13]Lactate production from [C -13]glucose, with no detectable uptake of [C-13]alanine, indicated tha t energy production in H5 spheroids was primarily via glycolysis. No [ C-13]glucose utilization was detected in H4 spheroids, but uptake of a lanine and accumulation of labeled lactate, glutamate and glutamine in dicated oxidation via the tricarboxylic acid (TCA) cycle. Tumors of H4 cells were well perfused, unlike tumors of H5 cells which were highly necrotic. Following i.v. infusion with [C-13]alanine, [C-13]lactate a nd glutamate, evidence of oxidation via the TCA cycle, were observed i n H4 tumors. Thus the results obtained by P-31 and C-13 MRS correlated with the differentiation state of H4 and H5 spheroids and tumors.