title: 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.
abstract: 8-Hydroxyguanine (8OHG), 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 8OHG or BPDE by a bacterial suppressor tRNA (supF) forward mutation assay using a shuttle plasmid, pMY189. The introduction of a single 8OHG 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 8OHG-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 8OHG but not by BPDE in human cells.
authors.affiliation: Biology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo, Japan.
authors.forename: Arito
authors.initials: A
authors.lastname: Yamane
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sunaga
authors.forename: Takayuki
authors.initials: T
authors.lastname: Saitoh
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Shinmura
authors.forename: Kimio
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Murakami
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D019757:Carbon-Oxygen Lyases / Q000502:physiology; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043382:DNA-Formamidopyrimidine Glycosylase; D006147:Guanine / Q000031:analogs & derivatives* / Q000633:toxicity*; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000502:physiology*; D017354:Point Mutation; D014407:Tumor Cells, Cultured
chemical_list: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D043382:DNA-Formamidopyrimidine Glycosylase; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase