**6.1.3 Whole foods**

Several studies, including our own with colon cancer cells, have found that polyphenol rich plant extracts inhibit formation of SBs and 8-oxoGua induced by oxidantive agents (Ramos *et al.*, 2010a). Some plants, such as *Salvia officinalis L.* (sage), *Rosmarinus officinalis L.* (rosemary) and *Origanum vulgare L.* (oregano) have antioxidant properties that confer protection against oxidative DNA damage in colon cells as demonstrated by Aherne et al., (2007).

Green tea is rich in polyphenolic antioxidants and their effects on health are the subject of several studies. Green tea decreased DNA oxidation in lymphocytes, colonocytes and hepatocytes when rats ingested 6.5 mg/kg bw per day, 5 days of tea extract (Kager et al., 2010). Evidences of genoprotective effects of green tea appear not only from in vitro and in vivo studies, but also from human supplementation trials. Human lymphocytes isolated from healthy volunteers that took 2 x 150 ml/d of 1% (w/v) green tea showed a decrease of basal oxidation-induced DNA damage with and without FPG enzyme (Han *et al.*, 2011). One of the main constituents of green tea is (-)-epigallocatechin-3-gallate (EGCG) that could be responsible for their beneficial effects. In human peripheral leucocytes treatement with low EGCG concentrations (2-100µM) decreased both bleomycin-induced breaks and endonuclease III sensitive sites (Glei and Pool-Zobel, 2006).

Apple is one of the most consumed fruit, therefore is an important source of polyphenols in humans. Their chemoprotective effects have been shown in vitro and in vivo studies (Koch et al., 2009; Veeriah et al., 2008). Apple juice has been found to possess antioxidant and antiproliferative activities as well as the ability to increase the expression of phase II gene glutathione S-transferase T2 (GSTT2) in human colon cells (Petermann et al., 2009). Apple extract can also protect against oxidative-induced DNA damage in human colon cells, such as LT97 (Miene (Miene *et al.*, 2009), HT29, HCT115 and CaCo-2 cells (McCann et al., 2007; Schaefer et al., 2006). Also, grape juices exhibit antigenotoxic activity (Dani et al., 2009).

The anticarcinogenic properties of olive oil have been attributed to the presence of phenolic compounds. Fabiani et al., (2008) reported that some of its isolated compounds (e.g. hydroxytyrosol, [3,4-dyhydroxyphenyl-ethanol (3,4-DHPEA)] and a complex mixture of phenols extracted from virgin olive oil) protected against H2O2 in human peripheral blood mononuclear cells and promyelocytic leukemia cells (HL60). These results have a great impact not only because of the high level of protection observed (between 80 and 90%) but also because, according to the authors, the concentrations tested could easily be reached with normal intake of olive oil.

Annatto is a native shrub from Tropical America, whose seeds are a rich source of carotenoids, such as bixin, norbixin and phytoene and have antigenotoxic effects against oxidative DNA damage (Kovary et al., 2001).

Results from human intervention trials have demonstrated the protective effect of isolated compounds as well as fruits and vegetables in peripheral lymphocytes. Pool-Zobel *et al.*, (1997) showed a decrease in pyrimidine oxidation during supplementation with carrot juice. Porrini and Riso, (2000) reported that supplementation with tomato that is rich in lycopene, increase protection against H2O2-induced DNA damage in lymphocytes. Also a diet rich in fruit and vegetables for 14 days showed a DNA protection from oxidative damage in lymphocytes (Thompson et al., 1999). Broccoli intake also decreases oxidative DNA damage in smokers and nonsmokers (Riso *et al.*, 2009). In a recent study, Sprague-Dawley rats fed with a wild-blueberry diet or a control diet for four or eight weeks were used to assess the effect of the consumption of this fruit on the resistance to H2O2-induced DNA damage. After treatment period, lymphocytes were exposed, ex vivo, to H2O2 and it was observed that wild-blueberry diet did not change antioxidant capacity in lymphocytes after eight weeks of treatment, but increased DNA protection against oxidative damage (Del Bo et al., 2010). Dulebohn et al., (2008) using the same animal model, reported that blueberries consumption for 3 weeks increase GST activity and decrease oxidative DNA damage in the liver. However, contrarily to in vitro studies, blueberries consumption did not significantly increase phase II enzyme activities in short-term supplementation times.

As described above, many isolated compounds and some plants showed genoprotective effects in several experimental models, however it is important to keep in mind that these dietary agents can also induce DNA damage in certain conditions. The balance between the genoprotective and genotoxic effects of dietary agents is dependent on their concentration, incubation period and types of cells (Rusak et al., 2010).

### **6.2 Effect of diet on prevention of alkylating DNA damage**

Alkylation of DNA can be an important initial step in cancer formation. High levels of alkylating damage have been found in human colorectal DNA where high incidence of tumours have been observed (Hall *et al.*, 1991; Povey *et al.*, 2000). To assess antigenotoxic effects of diet against alkylating damage, several experimental models have been developed. Among them, colon tumours induction in rodent models, with carcinogenic chemicals such as 1,2-dimethylhydrazine (DMH) or azoxymethane (AOM) are the most used, and they are believed to be representative of colon carcinogenesis in humans (Barth et al., 2005).
