| First Author | Cao Z | Year | 2016 |
| Journal | Cancer Lett | Volume | 372 |
| Issue | 2 | Pages | 219-25 |
| PubMed ID | 26801745 | Mgi Jnum | J:231472 |
| Mgi Id | MGI:5771613 | Doi | 10.1016/j.canlet.2016.01.007 |
| Citation | Cao Z, et al. (2016) Uridine homeostatic disorder leads to DNA damage and tumorigenesis. Cancer Lett 372(2):219-25 |
| abstractText | Uridine is a natural nucleoside precursor of uridine monophosphate in organisms and thus is considered to be safe and is used in a wide range of clinical settings. The far-reaching effects of pharmacological uridine have long been neglected. Here, we report that the homeostatic disorder of uridine is carcinogenic. Targeted disruption (-/-) of murine uridine phosphorylase (UPase) disrupted the homeostasis of uridine and increased spontaneous tumorigenesis by more than 3-fold. Multiple tumors (e.g., lymphoma, hepatoma and lung adenoma) occurred simultaneously in some UPase deficient mice, but not in wild-type mice raised under the same conditions. In the tissue from UPase -/- mice, the 2'-deoxyuridine,5'-triphosphate (dUTP) levels and uracil DNA were increased and p53 was activated with an increased phospho-Ser18 p53 level. Exposing cell lines (e.g., MCF-7, RKO, HCT-8 and NCI-H460) to uridine (10 or 30 microM) led to uracil DNA damage and p53 activation, which in turn triggered the DNA damage response. In these cells, phospho-ATM, phospho-CHK2, and phospho-gammaH2AX were increased by uridine. These data suggest that uridine homeostatic disorder leads to uracil DNA damage and that pharmacological uridine may be carcinogenic. |
