Unexpectedly Weak Impacts of Decreased p53 and Retinoblastoma Protein Levels on Mutagenesis by 8-Oxo-7,8-dihydroguanine (8-Hydroxyguanine)

抄録

The loss of tumor suppressor proteins, p53 and retinoblastoma (Rb), causes genomic instability. 8-Oxo-7,8-dihydroguanine (G^O, 8-hydroxyguanine) is a major oxidatively damaged base that induces G:C→T:A transversions in cells. In this study, the effects of p53 and Rb reductions on the mutagenicity of G^O in DNA were investigated, using a supF shuttle plasmid propagated in human U2OS and HT1080 cells. The p53 and Rb proteins were individually knocked-down by siRNAs, and then the plasmid DNA containing G^O was introduced into the knocked-down cells. The knock-downs of p53 and Rb had quite weak effects on mutagenesis by G^O in the shuttle plasmid. These results suggested that p53 and Rb minimally affect the G^O-induced mutagenic processes in living cells.