The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effect of uridine on response of 5-azacytidine-resistant human leukemic cells to inhibitors of de novo pyrimidine synthesis.

A uridine-cytidine kinase-deficient human promyelocytic leukemic subline (HL-60-5-aza-Cyd) has been isolated which is highly resistant to the antileukemic agent 5-azacytidine. Resistant cells exposed to 10(-5) M 5-azacytidine for 2 hr exhibit a marked reduction in both the total intracellular accumulation of 5-azacytidine (11.9 versus 156.0 pmol/10(6) cells) as well as its incorporation into RNA (3.1 versus 43.4 pmol/micrograms D-ribose) compared to the parent line. These biochemical changes are associated with nearly a 100-fold decrease in sensitivity to the growth inhibitory effects of 5-azacytidine (concentration of drug associated with a 50% reduction in cell growth, 3.5 X 10(-5) versus 5.0 X 10(-7) M). 5-Azacytidine-resistant cells exhibit cross-resistance to 3-deazauridine, 6-azauridine, and 5-fluorouridine, but not to 1-beta-D-arabinofuranosylcytosine, 2'-deoxyazacytidine, or 5-aza-1-beta-D-arabinofuranosylcytosine. Coadministration of 50 microM uridine prevented depletion of pyrimidine nucleoside triphosphates and inhibition of colony formation of HL-60 cells exposed to 3 mM N-(phosphonacetyl)-L-aspartate) or 5 X 10(-6) M pyrazofurin but was not capable of protecting HL-60-5-azacytidine under the same conditions. This uridine concentration was also able to restore control colony formation to normal human bone marrow progenitor cells (granulocyte-macrophage colony-forming units) exposed to de novo pyrimidine biosynthetic blockade. These in vitro studies suggest that 5-azacytidine resistant cells lacking the pyrimidine salvage pathway enzyme uridine-cytidine kinase may be selectively vulnerable to a regimen using pyrimidine antagonists administered in conjunction with the naturally occurring nucleoside uridine.[1]

References

 
WikiGenes - Universities