Adenosine deaminase and adenosine kinase in rat hepatomas and kidney tumours.
Adenosine deaminase and adenosine kinase have been measured in rat liver, 12 transplantable hepatomas, regenerating, foetal and neonatal liver, adult and neonatal rat kidney and 2 transplantable kidney tumours. Adenosine, deaminase activity, relative to the normal liver value, was elevated 2-4 fold in hepatomas of rapid growth rate, was in the normal range in more slowly growing hepatomas and in regernerating liver, and was low in foetal and neonatal liver. Adenosine kinase activity was decreased, relative to rat liver values, in all the hepatomas; activity of this enzyme gave a negative correlation with tumour growth rate. Kinetic properties of the two enzymes were examined in partially purified preparations. Adenosine deaminases from both liver and rapidly growing hepatoma 3924A were subject to weak product inhibition by inosine. Adenosine kinase from liver and hepatoma 3924A was inhibited by the reaction products ADP and AMP, and the enzyme was also subject to excess substrate inhibition by concentrations of ATP in excess of 1 mM. In rat hepatoma cell lines growing in culture, the toxicity of adenosine correlated inversely with the ratio of adenosine deaminase activity to adenosine kinase activity. Chromatographic measurements showed that hepatoma cells incorporated less extracellular adenosine into their adenine nucleotide pools than did isolated liver cells. These results indicate that increased adenosine deaminase activity and decreased adenosine kinase activity may confer a selective advantage upon the cancer cell.
D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D000248:Adenosine Kinase / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D002454:Cell Differentiation; D002478:Cells, Cultured; D007680:Kidney Neoplasms / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology*; D008115:Liver Regeneration; D008297:Male; D009374:Neoplasms, Experimental / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution
D010770:Phosphotransferases; D000248:Adenosine Kinase; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine