**9. Acknowledgements**

The authors would like to thank Katharine Martin, Neena Tierney, Peter Lyte, Dara Miller, Thierry Oddos, Karien Rodriguez and Dr. Balz Frei (Linus Pauling Institute, Oregon State University) for research and discussions on Feverfew PFE.

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**25** 

*Japan* 

**Food Factors and Oxidative** 

Takeshi Hirano1 and Kazuyoshi Tamae2

*Engineering, The University of Kitakyushu,* 

**DNA Damage / DNA Repair Systems** 

*1Department of Life and Environment Engineering, Faculty of Environmental* 

*2Division of Teacher Training, Faculty of Education and Culture, University of Miyazaki,* 

8-Oxoguanine (7, 8-dihydro-8-oxoguanine, abbreviated as 8-oxo-Gua), a form of oxidized guanine, is a mutagenic lesion formed spontaneously in the genomic DNA of aerobic organisms (Fig. 1) and by the actions of exogenous factors, such as ionizing radiation, chemical pollutants, heavy metals, food factors, and bacteria. 8-Oxo-Gua induces GC-to-TA transversion type point mutations [1]. Point mutations generated via oxidative DNA damage are involved in cancer development, because mutations are a common feature of human cancers. Therefore, 8-oxo-Gua is considered to be involved in carcinogenesis. In this context, studies of 8-oxo-Gua have significant implications for understanding the underlying mechanisms of mutation-associated diseases, including cancer [2]. Although 8 oxo-Gua is not necessarily the most abundant form of oxidative DNA damage, it has been the most extensively studied, because it is quite easily measured by a method utilizing HPLC coupled with electrochemical detection in laboratories [3, 4]. The presence of 8-oxo-Gua and 8-oxoadenine (8-oxo-Ade) in mutagenic oxidized DNA products has been extensively studied, and their frequencies of generation in mammalian DNA and degrees of mutagenicity are similar [5-8]. The relative focus-forming activity, which indicates the

mutation inducibility, of 8-oxo-Gua and 8-oxo-Ade were reportedly ~1% [7, 8].

is formed by hydroxylation of guanine at the C-8 position.

Fig. 1. Structure of 7, 8-dihydro-8-oxoguanine or 8-hydroxyguanine (8-OH-Gua). 8-Oxo-Gua

Extensive efforts have been made to clone the repair enzymes for 8-oxo-Gua. The first information was obtained from the studies of an enzyme, formamidopyrimidine DNA glycosylase (Fpg or MutM), which excises 8-oxo-Gua, 2, 6-diamino-4-hydroxy-5 formamidopyrimidine (FapyGua), and 4, 6-diamino-5-formamidopyrimidine (FapyAde)

**1. Introduction** 

Zhang, Y., Talalay, P., Cho, C. G., Posner, G. H., 1992. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A 89, 2399-2403.
