|Title:||Profiling ribonucleotide and deoxyribonucleotide pools perturbed by gemcitabine in human non-small cell lung cancer cells||Authors:||Guo, Jian-Ru
Lam, Christopher Wai Kei
Wong, Vincent Kam Wai
|Issue Date:||2016||Start page/Pages:||37250||Source:||Scientific Reports||Abstract:||
In this study, we investigated the dosage effect of gemcitabine, an inhibitor of ribonucleotide reductase (RR), on cellular levels of ribonucleotides and deoxyribonucleotides using high performance liquid chromatography-electrospray ionization tandem mass spectrometric method. As anticipated, after 4-h incubation of non-small cell lung cancer (A549) cells with gemcitabine at 0.5 and 2 mu M, there were consistent reductions in levels of deoxyribonucleoside diphosphates (dNDP) and their corresponding deoxyribonucleoside triphosphates (dNTP). However, after 24-h exposure to 0.5 mu M gemcitabine, the amounts of dNTP were increased by about 3 fold, whereas cells after 24-h 2 mu M gemcitabine treatment exhibited deoxycytidine diphosphate (dCDP), deoxyadenosine diphosphate (dADP) and deoxyguanosine diphosphate (dGDP) levels less than 50% of control values, with deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP) returning to the control level. Using cell cycle analysis, we found that 24-h incubation at 0.5 mu M gemcitabine resulted in a significant increase in S phase arrest, while 2 mu M treatment increased G0/G1 population. Our data demonstrated the correlation between the level of RR and the increased levels of dNTPs in the group of 0.5 mu M treatment for 24-h with a markedly reduced level of dFdCTP. Accordingly, we proposed that the dosage of dFdC could determine the arrested phase of cell cycle, in turn affecting the recovery of dNTPs pools.
|Appears in Collections:||分子醫學研究所|
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