Metabolism of hepatomas of different growth rates in situ and during ischemia.

In freeze-clamped rat liver and in hepatomas 9618-A and 5123-D (slower-growing) and 3924-A (rapidly growing), the initial concentrations and time course of changes during ischemia of adenine nucleotides, glucose, láclate, pyruvate, glutamate, 2-oxoglutarate, 3-hydroxybutyrate, acetoacetate, acetyl-CoA, acyl-CoA, glycerides, phospholipid, and total lipid were measured. Initial samples of the tissues were taken under anesthesia within 2 sec after severance of blood vessels, and subsequent samples were obtained during the ensuing ischemia up to 10 min. In hepatomas 5123-D and 3924-A, the initial concentrations of ATP, total adenine nucleotides, and the ATP/ADP ratio were markedly lower than those in livers. During ischemia in liver and in 5123-D and 9618-A, the concentrations of ATP, total adenine nucleotides, and the ATP/ADP ratio decreased while AMP levels increased. In the rapidly growing hepatoma, ischemia did not change ATP or AMP concentrations. The glucose and pyruvate concentrations were lower in all hepatomas than in liver. During ischemia, glucose levels increased in livers and in slow-growing hepatoma 9618-A but were not appreciably altered in the 2 other hepatomas. Initial láclate and glutamale concenlralions were much higher in Ihe rapidly growing hepaloma than in liver or in slower growing lumors; the concenlralion of 2-oxoglularale was low in all lumors. The ralios of Ihe initial concentralions of lactate/pyruvale and glutamate/2-oxoglutarate increased in hepatomas in parallel wilh growlh rale. Acelyl-CoA, acyl-CoA, lolal glycerides, phospholipids, and lolal lipids in 3924-A were 20 lo 50% of values observed in liver. In ischemia, Ihe concentralions of acyl-CoA increased in liver bul did noi change in Ihe hepaloma; Ihe acelyl-CoA, glyceride, phospholipid, and lolal lipid conlenl did noi change eilher in liver or in 3924-A. The inilial concenlralion of kelone bodies in fed rals was in Ihe same range in Ihe slower-growing tumors as in liver; however, it was low in the rapidly growing tumor. In slarvalion, Ihe lotal ketone and 3-hydroxybutyrale concenlralions increased over 10-fold in all lissues.