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Review
. 2006 May;82(4):127-41.
doi: 10.2183/pjab.82.127.

8-Hydroxyguanine: From its discovery in 1983 to the present status

Susumu Nishimura  1
Affiliations
Review

8-Hydroxyguanine: From its discovery in 1983 to the present status

Susumu Nishimura. Proc Jpn Acad Ser B Phys Biol Sci. 2006 May.

Abstract

8-Hydroxyguanine (8-OH-G) was discovered in 1983 in our laboratory at the National Cancer Center Research Institute, Tokyo. Since it could be formed in DNA not only in vitro but also in vivo by oxygen radical forming agents, we immediately hypothesized the importance of this discovery in connection with its biological consequence. Further intensive efforts by us from 1983 to 1990 confirmed that 8-OH-G is a highly significant oxidated DNA lesion involved in mutation and/or carcinogenesis in mammals, including humans. With the subsequent entry of many investigators to this research field the number of publications on 8-OH-G increased exponentially, reaching more than several thousands by the end of 2005. In this article, a summary is given of the important works carried out in the early days, and further notable contributions by many investigators are reviewed, focusing on 8-OH-G in the mammalian system. A special emphasis is given to research on knockout mice that are deficient in genes involved in the repair systems of the 8-OH-G lesion. Lastly, our own recent work is summarized involving a one-year carcinogenesis study of Ogg1 (the gene for 8-OH-G specific glycosylase/AP lyase) knockout mice that have been exposed to oxidative stress.

Keywords: 8-Hydroxyguanine; DNA repair; Mut M; mutagenesis, carcinogenesis; oxygen radical.

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Figures

Fig. 1.
Fig. 1.
Structure and unique UV spectra of 8-hydroxyisopropylidenguanosine.
Fig. 2.
Fig. 2.
Formation of 8-OH-G in DNA by oxygen radical-forming agents.
Fig. 3.
Fig. 3.
Detection of 8-OH-G in mouse liver DNA by HPLC-coupled electrochemical detection system.
Fig. 4.
Fig. 4.
Glycosylase and nicking assay for MutM protein by using synthetic deoxyribopolynucleotide having 8-OH-G.
Fig. 5.
Fig. 5.
Conformation of 8-hydroxyguanine obtained by ab initio molecular orbital method. Map of electrostatic potential (ESP) at the molecular surface, 1.5 Å distant from van der Waals spheros. Dot: red, 9 ≦ ESP; pink, 3 ≦ ESP<9; yellow, −3
Fig. 6.
Fig. 6.
Tautomeric form of 8-OH-G.
Fig. 7.
Fig. 7.
Formation of base pairs of 8-OH-G with C or A in the opposite strands.
Fig. 8.
Fig. 8.
DNA repair systems for 8-OH-G in E. coli and mammalian cells. The names of the enzymes in parenthesis are that from mammalian cells.
Fig. 9.
Fig. 9.
Mutation spectra of gpt gene from liver of gpt/Ogg1 mutant mice which had been exposed to KBrO3, followed by partial hepatectomy.
See this image and copyright information in PMC

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