Suppressive activities of OGG1 and MYH proteins against G:C to T:A mutations caused by 8-hydroxyguanine but not by benzo[a]pyrene diol epoxide in human cells in vivo

Arito Yamane, Kazuya Shinmura, Noriaki Sunaga, Takayuki Saitoh, Satoru Yamaguchi, Yumi Shinmura, Kimio Yoshimura, Hirokazu Murakami, Yoshihisa Nojima, Takashi Kohno, Jun Yokota

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Abstract

8-Hydroxyguanine (80HG), an oxidatively damaged base, and benzo[a]pyrene-diol-epoxide (BPDE), a metabolite of benzo[a]pyrene found in cigarette smoke, are thought to be major causes for G:C to T:A transversions in DNA of human cells. In this study, we assessed the abilities of OGG1, MYH and APE1 proteins, which are components of a base excision repair pathway, to suppress G:C to T:A transversions caused by 80HG or BPDE by a bacterial suppressor tRNA (supF) forward mutation assay using a shuttle plasmid, pMY189. The introduction of a single 80HG residue at position 159 of the supF gene and treatment with BPDE led to a 65- and 34-fold increase in mutation frequencies of the pMY189 plasmid, respectively, after replication in the NCI-H1299 human lung cancer cell line. G:C to T:A transversions were predominantly induced in these plasmids. Both the mutation frequency of the 80HG-containing plasmid in NCI-H1299 cells and the occurrence of G:C to T:A transversions at position 159 in the supF gene were significantly reduced by overexpression of OGG1 and MYH proteins, but not by that of APE1 protein. In contrast, neither mutation frequency nor the occurrence of G:C to T:A transversion of the BPDE-treated plasmid was reduced by overexpression of OGG1, MYH and APE1 proteins. These results indicate that OGG1 and MYH function as suppressors for G:C to T:A transversions by 80HG but not by BPDE in human cells.

Original languageEnglish
Pages (from-to)1031-1037
Number of pages7
JournalCarcinogenesis
Volume24
Issue number6
Publication statusPublished - 2003 Jun 1

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Yamane, A., Shinmura, K., Sunaga, N., Saitoh, T., Yamaguchi, S., Shinmura, Y., Yoshimura, K., Murakami, H., Nojima, Y., Kohno, T., & Yokota, J. (2003). Suppressive activities of OGG1 and MYH proteins against G:C to T:A mutations caused by 8-hydroxyguanine but not by benzo[a]pyrene diol epoxide in human cells in vivo. Carcinogenesis, 24(6), 1031-1037.