**3. Alcohol and 8-oxo-Gua / OGG1**

Alcohol consumption has been associated with a variety of human cancers for several centuries. Recent studies revealed that alcohol consumption is associated with an increase in breast cancer incidence in women [23, 24], esophageal cancer [25], and colorectal cancer [26, 27]. On the other hand, the cancer-preventive effects of alcohol drinking have also been reported. It is well known that moderate consumption of wine may prevent some types of cancers [28-30]. These studies concerning wine consumption suggested that anti-oxidant agents, such as polyphenols, including catekin, quercetin and resveratrol, contributed to the cancer–preventive effect of wine [31]. Thus, anti-oxidant agents seem to play a key role in the beneficial effects of wine. It was also suggested that resveratrol could reduce the localized estrogen production that plays a crucial role in the development of breast cancer [32]. On the other hand, for alcoholic beverages other than wine, a cohort study suggested that alcohol (spirits and beer) consumption was associated with a decrease in the risk of renal cell carcinoma in male smokers [33]. A matched case-control study reported a similar result, in which regular, moderate alcohol (beer, wine, and spirits) consumption was associated with a decreased probability of leukoplakia occurrence, with respect to occasional or no alcohol consumption [34]. These results are not conclusive, but suggest that other

from the DNA of *Escherichia coli* [9]. This enzyme has an activity to process the resulting abasic (AP) site, by cleaving both the 3'- and 5'-phosphodiester bonds by successive β- and δ-eliminations [10-12]. In 1996, an Fpg homologue was identified in *Saccharomyces cerevisiae* [13, 14]. This was the first report of an 8-oxoguanine DNA glycosylase 1 (OGG1). In the following year, mammalian (human and other mammals) homologues of OGG1 were identified and cloned [15-21]. 8-Oxo-Gua is efficiently removed from DNA via the short-

Among the environmental factors that are related to human diseases, food factors have a large influence on human health. To understand the mechanisms of food-related carcinogenesis, the roles of 8-oxo-Gua have been investigated in relationship with food factors. In this review article, we will focus on and describe the relationship between food

Food factors have been extensively investigated in association with oxidative DNA damage and its repair systems. Some food factors, such as aminoazo dyes, are known inhibitors of OGG1 expression. Aminoazo dyes were previously used as artificial color additives to food. Some of them, such as *N*-methyl-4-aminoazobenzene, *N*, *N*-dimethyl-4-aminoazobenzene, and 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), are hepato-carcinogenic. We previously analyzed the effects of 3'-MeDAB on 8-oxo-Gua repair systems in rodent livers, and reported that 3'-MeDAB increased 8-oxo-Gua generation and decreased OGG1 expression, possibly by cleaving the protein [22]. These results suggested that the liver carcinogenicity of 3'-MeDAB was due to an increase in 8-oxo-Gua generation via 3'-MeDAB-

The use of 3'-MeDAB as a food additive is now prohibited. However, other types of azo dyes are still being used. Therefore, more research is needed to define the effects of azo dyes

Alcohol consumption has been associated with a variety of human cancers for several centuries. Recent studies revealed that alcohol consumption is associated with an increase in breast cancer incidence in women [23, 24], esophageal cancer [25], and colorectal cancer [26, 27]. On the other hand, the cancer-preventive effects of alcohol drinking have also been reported. It is well known that moderate consumption of wine may prevent some types of cancers [28-30]. These studies concerning wine consumption suggested that anti-oxidant agents, such as polyphenols, including catekin, quercetin and resveratrol, contributed to the cancer–preventive effect of wine [31]. Thus, anti-oxidant agents seem to play a key role in the beneficial effects of wine. It was also suggested that resveratrol could reduce the localized estrogen production that plays a crucial role in the development of breast cancer [32]. On the other hand, for alcoholic beverages other than wine, a cohort study suggested that alcohol (spirits and beer) consumption was associated with a decrease in the risk of renal cell carcinoma in male smokers [33]. A matched case-control study reported a similar result, in which regular, moderate alcohol (beer, wine, and spirits) consumption was associated with a decreased probability of leukoplakia occurrence, with respect to occasional or no alcohol consumption [34]. These results are not conclusive, but suggest that other

patch base excision repair (BER) pathway initiated by OGG1.

factors and 8-oxo-Gua / 8-oxo-Gua repair systems.

**2. Aminoazo dyes and 8-oxo-Gua / OGG1** 

induced downregulation of OGG1 expression.

**3. Alcohol and 8-oxo-Gua / OGG1** 

on human health.

components of alcoholic beverages (including wine) besides polyphenols may be responsible for the beneficial effects on human health.

The evidence that not only wine but also spirits and beer have cancer-preventive effects prompted us to investigate the molecular mechanisms of these effects of alcohol consumption due to factors other than polyphenols. In fact, recent evidences have suggested that the protective effects of red wine on cancer or cardiovascular diseases were not a consequence of the anti-oxidant capacity of alcohol [35, 36]. Arendt et al. reported the reduction of DNA damage as another mechanism of the cancer-preventive function of wine [35].

In this context, we analyzed the 8-oxo-Gua accumulation level in DNA and its repair ability (8-oxo-Gua nicking activity and mouse OGG1 (mOGG1) expression) in the livers of mice treated with 3'-MeDAB, a well known hepato-carcinogen as described above, and / or ethanol, to examine the effects of alcohol consumption on carcinogenesis (Fig. 2A) [37]. The method used to determine the 8-oxo-Gua nicking activity was described elsewhere [38]. In the study, we found that 12% ethanol reduced the 3'-MeDAB-induced 8-oxo-Gua accumulation (Fig. 2B). Moreover, the 8-oxo-Gua repair activity showed a decreasing tendency in 3'-MeDAB-treated mouse livers with 12% ethanol administration, without any significant differences (Fig. 2C). The decrease in the 8-oxo-Gua repair activity seems to be a reasonable consequence of the lower 8-oxo-Gua levels. Since we speculated that OGG1 fragmentation was a key event for 3'-MeDAB-induced 8-oxo-Gua accumulation [22], we predicted that OGG1 fragmentation might be inhibited by ethanol intake, as in the inhibition of the increase in 8-oxo-Gua levels. However, 12% ethanol intake failed to inhibit the 3'- MeDAB-induced fragmentation of OGG1 (groups D, E, and F in Fig. 2D). The observations indicated that ethanol intake reduced 8-oxo-Gua accumulation, without affecting the function of OGG1. However, since other enzymes besides OGG1 can reportedly repair 8 oxo-Gua [39], we speculate that ethanol consumption might induce these 8-oxo-Gua repair systems to reduce the 8-oxo-Gua level.
