Adenosine deaminase and adenosine kinase in rat hepatomas and kidney tumours

Abstract

Summary.-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 regenerating 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.

Expression level of adenosine kinase in rat tissues. Lack of phosphate effect on the enzyme activity.

“…heart > skeletal muscle ( Table 2). Similar results for rat tissues were reported previously [29]. In human tissues almost equivalent levels of AK activity were found in liver, kidney, brain cortex and pancreas [30].…”

Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model

“…Two genes including Zbtb20 34,35 and Ankrd17 36,37 are involved in hepatocyte differentiation and maturation, while Zbtb20 is a transcription factor that represses the expression of α-fetoprotein, a widely used biomarker used for HCC surveillance. The Setd2 TS gene 38 and the putative TS genes Adk 39 , Dpyd 40,41 , Mll5 42 and Nfia 43,44 were also identified as potential driver genes for HCC, although there is no published evidence they are involved in HCC. Six driver genes also regulate hepatic metabolism with Pten 45 , Gsk3b 46 , Adk 47,48 , Zbtb20 49 and Ghr 50,51 regulating lipid and glucose metabolism, and Dpyd controling pyrimidine catabolism in hepatocytes.…”

Adenosine acts as a chemoprotective agent by stimulating G-CSF production: A role for A1 and A3 adenosine receptors

“…Pospisil et al (1993Pospisil et al ( , 1995Pospisil et al ( , 1998 showed that administration of adenosine monophosphate (AMP) combined with dipyridamole and G-CSF, prior to radiation, led to a radioprotective effect by the stimulation of hematopoiesis in the bone marrow and spleen of the treated mice. Jackson et al (1978) and Epstein and Preisler (1984) treated mice with the antimetabolite 6-thioguanine and demonstrated that adenosine exerted a protective effect on myeloid progenitor cells. In these studies, adenosine or AMP was administered, but at a much higher daily dose (500 mg/kg body weight) than used in the present work.…”