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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 7308501, 11 pages
https://doi.org/10.1155/2017/7308501
Research Article

Mutation Spectrum Induced by 8-Bromoguanine, a Base Damaged by Reactive Brominating Species, in Human Cells

1Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
2Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa 078-8510, Japan

Correspondence should be addressed to Kazuya Shinmura

Received 17 May 2017; Revised 23 August 2017; Accepted 6 September 2017; Published 30 September 2017

Academic Editor: Janusz Gebicki

Copyright © 2017 Kazuya Shinmura et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

To date, the types of mutations caused by 8-bromoguanine (8BrG), a major base lesion induced by reactive brominating species during inflammation, in human cells and the 8BrG repair system remain largely unknown. In this study, we performed a supF forward mutation assay using a shuttle vector plasmid containing a single 8BrG in three kinds of human cell lines and revealed that 8BrG in DNA predominantly induces a G → T mutation but can also induce G → C, G → A, and delG mutations in human cells. Next, we tested whether eight kinds of DNA glycosylases (MUTYH, MPG, NEIL1, OGG1, SMUG1, TDG, UNG2, and NTHL1) are capable of repairing 8BrG mispairs with any of the four bases using a DNA cleavage activity assay. We found that both the SMUG1 protein and the TDG protein exhibit DNA glycosylase activity against thymine mispaired with 8BrG and that the MUTYH protein exhibits DNA glycosylase activity against adenine mispaired with 8BrG. These results suggest that 8BrG induces some types of mutations, chiefly a G → T mutation, in human cells, and some DNA glycosylases are involved in the repair of 8BrG.