Application of artificial neural network to investigate the effects of 5-fluorouracil on ribonucleotides and deoxyribonucleotides in HepG2 cells

作者: Jianru Guo , QianQian Chen , Christopher Wai Kei Lam , Caiyun Wang , Vincent Kam Wai Wong

DOI: 10.1038/SREP16861

关键词: Deoxyuridine monophosphateDeoxyuridineRibonucleotideBiologyDeoxyuridine TriphosphateDeoxyadenosine triphosphateCytosine nucleotideGuanosine triphosphateBiochemistryDeoxyribonucleotides

摘要: Endogenous ribonucleotides and deoxyribonucleotides are essential metabolites that play important roles in a broad range of key cellular functions. Their intracellular levels could also reflect the action nucleoside analogues. We investigated effects 5-fluorouracil (5-FU) on ribonucleotide deoxyribonucleotide pool sizes cells upon exposure to 5-FU for different durations. Unsupervised supervised artificial neural networks were compared comprehensive analysis global responses 5-FU. As expected, deoxyuridine monophosphate (dUMP) increased after incubation due inhibition thymine (TMP) synthesis. Interestingly, accumulation dUMP not lead triphosphate (dUTP) diphosphate (dUDP). After initial fall deoxythymidine (TTP) concentration, its level recovered from 48 h 5-FU, although (TDP) TMP continued decrease with control group. These findings suggest treatment caused unexpected changes purine polls, such as increases deoxyadenosine (dATP), adenosine-triphosphate (ATP), guanosine (GTP) pools. Further elucidation mechanism causing these should enhance development strategies will increase anticancer activity while decreasing resistance.

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