Inhibition of methylation of DNA and tRNA by adenosine in an adenosine-sensitive mutant of the baby hamster kidney cell line

Differential response of Drosophila cell lines to extracellular adenosine

“…It was shown in some mammalian cells that accompanying increase in AMP and S-adenosylhomocysteine concentration may contribute to Ado cytotoxicity causing pyrimidine starvation and hypomethylation, respectively (Green and Chan, 1973;Skinner et al, 1986). In accordance we found that the inhibitor of adenosine kinase Itu prevented Ado-induced growth retardation of Cl.8þ cells pointing to the involvement of Ado phosphorylation in its toxic effect.…”

Role of elevated S-adenosylhomocysteine in rat hepatocyte apoptosis: Protection by betaine

“…These naïve hepatocytes were then exposed in vitro to agents that are known to increase intracellular SAH levels by exploiting the unique characteristic of the enzyme, SAH hydrolase, which catalyzes the reverse hydrolysis of SAH to adenosine and homocysteine. Incubations with SAHhydrolase inhibitor, or under conditions of excess adenosine and homocysteine either added alone or in combination have all been shown to generate increased intracellular SAH [24][25][26]32]. But in our study, we did not use homocysteine as an agent to achieve increased intracellular SAH levels but instead focused on adenosine.…”

“…More recent studies using various cell types that implicate increased adenosine toxicity via increased SAH levels have employed comparable adenosine concentrations as used by us [24,[26][27][28][29]42]. The mechanism of action of adenosine appears to be via its ability to act as a substrate for as well as an inhibitor of SAH hydrolase thereby elevating intracellular SAH.…”

“…In recent years there have been reports of increased intracellular SAH levels inducing apoptosis in many different cell types [23][24][25][26][27][28][29]. Therefore, we put forth the hypothesis that increased intracellular SAH generation may be responsible for hepatocyte apoptosis seen after ethanol administration.…”

“…We accomplished this undertaking by exploiting the unique characteristic of the enzyme SAH hydrolase-the only enzyme involved in SAH catabolism. Since SAH hydrolase catalyzes the reversible hydrolysis to adenosine and homocysteine with equilibrium of the reaction favoring the synthesis of SAH [30,31], altering the levels of its products (adenosine and/or homocysteine) has been shown to play a critical role in the control of tissue levels of SAH [24][25][26]32]. Therefore in this study, hepatocytes were exposed to varying concentrations of adenosine in order to promote the generation of SAH in order to increase intracellular SAH levels.…”