Uridine homeostatic disorder leads to DNA damage and tumorigenesis

• Published in: Cancer letters Vol. 372; no. 2; pp. 219 - 225
• Main Authors: Cao, Zhe, Ma, Jun, Chen, Xinchun, Zhou, Boping, Cai, Chuan, Huang, Dan, Zhang, Xuewen, Cao, Deliang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.03.2016; Elsevier Limited
• Subjects: Accreditation; Alzheimer's disease; Animals; Biosynthesis; Carcinogenesis; Carcinogens; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Deoxyribonucleic acid; Diabetic neuropathy; DNA; DNA Damage; Dose-Response Relationship, Drug; Genotype; Hematology, Oncology and Palliative Medicine; Homeostasis; Human subjects; Humans; Kinases; Mammals; MCF-7 Cells; Metabolism; Metabolites; Mice, Knockout; Neoplasms - etiology; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Nutrition research; p53; Phenotype; Phosphorylation; Plasma; Proteins; Rodents; Time Factors; Tumor Suppressor Protein p53 - metabolism; Tumorigenesis; Tumors; Up-Regulation; UPase knockout; Uracil - metabolism; Uracil DNA damage; Uridine - metabolism; Uridine - toxicity; Uridine homeostasis; Uridine phosphorylase; Uridine Phosphorylase - deficiency; Uridine Phosphorylase - genetics; dTTP; dUTP; dCDP; FLARE assay; Carcinogenesis; p53; UTP; Uracil DNA damage; DDR; UK; UDG; UPase-2; UDP; UPase knockout; mCEC; PRPP; Uridine homeostasis; DAPI; UPase; BER; PCE; dCTP; Uridine phosphorylase; UMP; ATM; dUMP; ATP; dTMP; CTP; ATR; TS; DNA damage response; 2′-deoxyuridine,5′ -triphosphate; ataxia telangiectasia mutated; ATM-Rad3-related; deoxycytidine 5′-diphosphate; 5′-monophosphate; base excision repair; 4′,6-diamidino-2-phenylindole; uridine 5′-diphosphate; uridine 5′-triphosphate; uridine phosphorylase; deoxyuridylate; deoxycytidine 5′-triphosphate; uridine kinase; thymidylate synthase; cytidine 5′-triphosphate; deoxythymidylate; uridine phosphorylase-2, a novel isoform; polychromatic erythrocytes; phosphoribosyl pyrophosphate; fragment length analysis using repair enzyme assay; mouse colon epithelial cells; adenosine triphosphate; deoxythymidine 5′-triphosphate; uracil DNA glycosylase

•Uridine homeostatic disorder induced by uridine phosphorylase knockout leads to DNA damage and spontaneous tumorigenesis.•Addition of uridine into culture medium causes uracil DNA damage and p53-mediated DNA damage response (DDR).•Pharmacological use of uridine may be carcinogenic, and the far-reac...