Aberrant oxidation is a property of many tumor cells. Oxidation of DNA 
precursors, i.e., deoxynucleotide triphosphates (dNTPs), as well as DNA is a 
major cause of genome instability. Here, we report that human DNA polymerase eta 
(h Poleta) incorporates oxidized dNTPs, i.e., 2-hydroxy-2'-deoxyadenosine 
5'-triphosphate (2-OH-dATP) and 8-hydroxy-2'-deoxyguanosine 5'-triphosphate 
(8-OH-dGTP), into DNA in an erroneous and efficient manner, thereby inducing 
various types of mutations during in vitro gap-filling DNA synthesis. When 
2-OH-dATP was present at a concentration equal to those of the four normal dNTPs 
in the reaction mixture, DNA synthesis by h Poleta enhanced the frequency of 
G-to-T transversions eight-fold higher than that of the transversions in control 
where only the normal dNTPs were present. When 8-OH-dGTP was present at an 
equimolar concentration to the normal dNTPs, it enhanced the frequency of A-to-C 
transversions 17-fold higher than the control. It also increased the frequency 
of C-to-A transversions about two-fold. These results suggest that h Poleta 
incorporates 2-OH-dATP opposite template G and incorporates 8-OH-dGTP opposite 
template A and slightly opposite template C during DNA synthesis. Besides base 
substitutions, h Poleta enhanced the frequency of single-base frameshifts and 
deletions with the size of more than 100 base pairs when 8-OH-dGTP was present 
in the reaction mixture. Since h Poleta is present in replication foci even 
without exogenous DNA damage, we suggest that h Poleta may be involved in 
induction of various types of mutations through the erroneous and efficient 
incorporation of oxidized dNTPs into DNA in human cells.