5-Hydroxyuracil Incision Activity Varies According to the Histological Grade of Non-muscle-invasive Bladder Cancer

Abstract

Objective: High levels of endonuclease III-like 1 (NTHL1) DNA glycosylase, which plays a role in the first step of the base excision repair pathway, has been related to cancer initiation and progression. 5-hydroxyuracil (5-OHU) oxidative base damage is a substrate for NTHL1 and endonuclease VIII-like 1 enzyme 1 (NEIL1) DNA glycosylases. This study investigates the association of 5-OHU incision activity with the risk of disease progression in patients with non-muscle-invasive bladder cancer (NMIBC) regarding grade and stage. Materials and Methods: During transurethral resection of 17 NMIBC patients, the papillary tumour before monopolar resection and healthy bladder mucosal tissue from the same person were obtained using cold cup biopsy. Both the normal mucosa and NMIBC tumour were pathologically confirmed. The histological grade and stage were also determined. The 5-OHU incision activity of all tissues was measured using a radiolabelled 5-OHU modified base containing DNA substrate. Results: 5-OHU incision activity was significantly higher in all high-grade NMIBC tissue extracts compared with the corresponding normal tissues (p=0.001). However, we found no significant difference in 5-OHU incision activity in low-grade NMIBC tissues (p=0.89). There was also a significant increase in 5-OHU incision activity at the Ta/T1 stage compared with the corresponding normal tissue (p=0.001). Conclusion: The increase in 5-OHU incision activity according to the histological grade of NMIBC tissue indicates that this activity (mainly performed by NTHL1 and NEIL1 DNA glycosylases) might play a role in NMIBC prognosis. Thus, it could be used as a potential prognostic biomarker for NMIBC.