Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8552375 | Reproductive Toxicology | 2018 | 9 Pages |
Abstract
Thymidylate synthase (TYMS) is a key enzyme in the de novo synthesis of 2â²-deoxythymidine-5â²-monophosphate (dTMP) from 2â²-deoxyuridine-5â²-monophosphate (dUMP). Our aim was to investigate the role of dTMP dysmetabolism via inhibition of TYMS by an inhibitor, 5-fluorouracil (5-FU) in the occurrence of neural tube defects (NTDs). We found that a high incidence of NTDs occurred after treatment with 5-FU at 12.5â¯mg/kg body weight. TYMS activity was significantly inhibited with decreased dTMP and accumulation of dUMP after 5-FU injection. The proliferation of neuroepithelial cells were markedly inhibited in NTDs compared with control. Expressions of proliferating cell nuclear antigen and phosphohistone H3 were significantly decreased in NTDs, while phosphorylated replication protein A2, P53 and Caspase3 were significantly increased in NTDs compared with control. These results indicated that inhibition of TYMS affected the balance between proliferation and apoptosis in neuroepithelial cells, which might shed some lights on the mechanisms involved in NTDs.
Related Topics
Life Sciences
Environmental Science
Health, Toxicology and Mutagenesis
Authors
Xiuwei Wang, Zhen Guan, Yanting Dong, Zhiqiang Zhu, Jianhua Wang, Bo Niu,