Altered oxidative metabolism is a property of many tumor cells. Oxidation of DNA 
precursors, i.e., dNTP pool, as well as DNA is a major source of mutagenesis and 
carcinogenesis. Here, we report the remarkable nature of human DNA polymerase 
eta that incorporates oxidized dNTPs into a nascent DNA strand in an efficient 
and erroneous manner. The polymerase almost exclusively incorporated 
8-hydroxy-dGTP (8-OH-dGTP) opposite template adenine (A) at 60% efficiency of 
normal dTTP incorporation, and incorporated 2-hydroxy-dATP (2-OH-dATP) opposite 
template thymine (T), guanine (G), or cytosine (C) at substantial rates. The 
synthetic primers having 8-hydroxy-G paired with template A or 2-hydroxy-A 
paired with template T, G, or C at the termini were efficiently extended. In 
contrast, human DNA polymerase iota incorporated 8-OH-dGTP opposite template A 
with much lower efficiency and did not incorporate 2-OH-dATP opposite any of the 
template bases. It did not extend the primers having the oxidized bases at the 
termini either. We propose that human DNA polymerase eta may participate in 
oxidative mutagenesis through the efficient and erroneous incorporation of 
oxidized dNTPs during DNA synthesis.