Purine and pyrimidine nucleotide patterns of normal, differentiating, and regenerating liver and of hepatomas in rats
Jackson, R.C.; Lui, M.S.; Boritzki, T.J.; Morris, H.P.; Weber, G.
Cancer Research 40(4): 1286-1291
1980
ISSN/ISBN: 0008-5472 PMID: 7053201 Document Number: 160581
The pattern of purine and pyrimidine nucleotides was elucidated in freeze-clamped preparations of normal liver; in hepatomas of very slow (9618A), intermediate (8999) and rapid (3924A) growth rates; in regenerating liver and in liver of neonatal rats. The ribonucleotide content was measured by high-pressure liquid chromatography, and that of the deoxyribonucleoside triphosphates was determined by enzymic assays. In the liver, the contents of dTTP, dCTP, dATP and dGTP were very low (1-5.1 nmol/g wet weight). The concentrations of deoxyribonucleoside triphosphates were increased relative to liver in all hepatomas and the rise correlated with the tumor growth rates. ATP concentration and total adenine nucleotide amounts were negatively correlated with tumor growth rate. The ATP level in hepatoma 3924A was 43% of the normal liver concentration. Contents of CTP and of total cytosine nucleotides were increased in all 3 liver tumors. The XMP content of hepatoma 3924A was 233% of that of normal liver and GMP concentration in all 3 hepatomas was above the liver values. There were no other consistent changes in the guanine and uracil nucleotide concentrations in the hepatomas. In the 24-h regenerating liver, the CTP and XMP levels were higher than normal liver values. The regenerating liver had increased uridine nucleotides and normal ATP concentration. In the liver of 6 day old rats, with the exception of a 27% increase in CTP level, the ribonucleotide contents did not differ from those of adult rat liver. In normal rat liver, a period of ischemia of up to 10 min resulted in extensive dephosphorylation of ATP and other nucleoside triphosphates, with the degraded material accumulating as monophosphates and nucleosides. Hepatoma 3924A (and the other hepatomas to a much lesser extent) possessed the ability to maintain ATP levels near normal values for 10 min of ischemia. This capability was lost following iodoacetate treatment, suggesting that the maintenance of a normal ATP level in hepatoma 392A during ischemia was associated with the high activity of anaerobic glycolysis in this tumor. Aspects of the pyrimidine and purine nucleotide pattern apparently are linked with transformation or progression in hepatomas of different growth rates. The pattern of deoxynucleoside triphosphate pools in rapidly growing differentiating and regenerating liver and in hepatoma 3924A shows that the concentrations of these key precursors of DNA biosynthesis are particularly increased in the tumor. This may confer selective advantages on the neoplastic cells.