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2-Hydroxyadenine (isoguanine) as oxidative DNA damage: its formation and mutation inducibility
1Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Abstract:
In our experiments we found that hydroxylation occurs at the C-2 position of adenine by oxygen radical treatment (Fe(2+)-EDTA) of dA, dATP, and single- and double-stranded DNA. This oxidatively damaged base, 2-hydroxyadenine (also known as isoguanine), was produced more efficiently in monomers than in polynucleotides. 2-Hydroxydeoxyadenosine triphosphate was incorporated opposite T and C in a DNA template by DNA polymerase alpha and only opposite T by the Klenow fragment. The Klenow fragment, DNA polymerases alpha and beta incorporated dTMP and other nucleotides opposite 2-OH-Ade in DNA templates in vitro in a sequence-dependent manner. These results suggest that the formation of 2-OH-Ade in DNA will induce mutations in cells.