To assess the functions of the three human MutT-type enzymes, MTH1, MTH2, and 
NUDT5, mutation induction by an oxidized form of dGTP, 
8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP; 
7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate), was examined using human 
293T cells treated with their specific siRNAs. Shuttle plasmid DNA containing 
the supF gene was first transfected into the cells, and then 8-OH-dGTP was 
introduced by means of osmotic pressure. Escherichia coli cells were transformed 
with the DNAs replicated in the treated cells. The knockdown of the MTH1, MTH2, 
and NUDT5 proteins increased the A:T --> C:G substitution mutations induced by 
8-OH-dGTP. In addition, the increase in the induced mutation frequency was more 
evident in the triple-knockdown cells. These results indicate that all three of 
the human MTH1, MTH2, and NUDT5 proteins act as a defense against the 
mutagenesis induced by oxidized dGTP.