The oxidative metabolic pattern of mouse hepatoma C954 as studied with C14-labeled acetates, propionate, octanoate, and glucose.

Weinhouse and co-workers (39-43) have estab lished that the Krebs tricarboxylic acid cycle operates in a variety of experimental tumors and that fatty acid oxidation, believed to be non existent in tumors (9), provides 2-carbon frag ments for continuous operation of this cycle in neoplastic tissues. Our studies with the mouse hepatoma C954, carried by mice of the C57-Leaden strain, also led us to conclude that the oxidation of octanoate by tumor tissue followed the same course as in normal tissues (4, 8). The labeling of acetoacetate, formed after incubation of tumor slices with octanoate-1-C14, was consistent with the mechanism of /3-oxidation-cleavage-condensation observed in normal tissues (4, 8). The present experiments were undertaken to determine whether any well defined derangement existed in the metabolism of a neoplastic tissue. Comparisons were made of normal mouse liver, host liver, and hepatoma CHÌ, all of which were allowed to oxidize radioactive substrates in vitro. Acetate-1-C14, acetate-2-C14, octanoate-1-C14, propionate-1-C14, pyruvate-2-C14, and uniformly la beled glucose were employed as substrates. In corporation of C14from the substrates into various intermediates was studied by a chromatographicautoradiographic technic. The present experi ments with hepatoma Cm fully confirm, in gen eral, the observations of Weinhouse and coworkers (39-42) and extend those observations to include, in the metabolic spectrum of tumor tissue, several reactions peripheral to the tri carboxylic acid cycle. Most reactions observed in