Bacillus Calmette-Guerin Increases Base Excision Repair in Bladder Cancer Cells

Abstract

Objective: Most patients with non-muscle-invasive bladder cancer (NMIBC) do not respond to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy and have high risk of NMIBC recurrence and progression. In addition to its therapeutic effect which increases the local immune response, BCG also exerts an anti-tumour effect by increasing oxidative stress, and producing reactive oxygen species and oxidative DNA damage in bladder cancer (BC) cells. The oxidative DNA damage is repaired by base excision repair (BER) mechanism. Thus, BER capacity of BC cells could be an important factor in response to BCG therapy. Effects of BCG on the activity of BER in BC transitional carcinoma cell line, T24 have been investigated. Materials and Methods: The uracil-initiated total BER and BER enzyme activities were measured in whole cell extracts with or without BCG treatment using a {[}gamma-32P] adenosine triphosphate-labelled 51-mer DNA substrates. Results: BCG treatment increased the activities of uracil-initiated total BER and BER enzymes, uracil DNA glycosylase and DNA polymerase beta in 6 h and 24 h repair periods and increased the activity of 8-oxoguanine DNA glycosylase in 6 h repair in T24 BC cell line. Conclusion: The enhanced BER activity in BC cells in response to BCG treatment could be an important factor in BCG resistance.