**6.3.1 Polyphenols**

254 Selected Topics in DNA Repair

of colonocytes (unpublished observations). Using the same experimental model, Sengupta *et al.*, (2004 and 2003) reported that tomato and garlic prevent ACFs, induced by AOM in rat colon. Tomato also decreased incidence and progression of 9,10-dimethyl benzanthracene (DMBA)-induced mouse skin tumours (De and Das, 2001). Intake of beer reduced ACF formation and protected against DNA damage induced by AOM in the rat colon mucosa (Nozawa et al., 2004). de Lima *et al.*, (2005) evaluated the effect of aqueous extract of propolis on the formation of DMH-induced ACF and DNA damage in rat colon. Propolis had no effect on ACF formation, however, modulation of DMH-induced DNA damage in colon cells was observed. At lower concentrations (12, 34 and 108 mg/Kg bw/day) aqueous extract of propolis decrease the level of DNA damage. However, the highest concentration (336mg/Kg bw/day) induced DNA damage in rat colon. Dietary agents such as, ginseng, lemon grass and propolis, have been found to inhibit DMH- and AOM-induced colon carcinogenesis and DNA damage in animal model (Bazo et al., 2002; Suaeyun *et al.*, 1997; Volate et al., 2005). Consumption of onion, blueberries (Boateng et al., 2007), and garbanzo beans (Murillo *et al.*, 2004) also decreased the number of AOM-induced ACFs in rats and

Some studies reported antigenotoxic effects of diet against alkylating DNA damage using cytogenetic assays (micronucleus assay) (Azevedo Bentes Monteiro Neto et al., 2011; Gurbuz *et al.*, 2009). Edenharder *et al.*, (1998) reported that sweet cherries, strawberries, cucumber, tomatoes, bananas, oranges, asparagus, yellow red peppers and specially spinach had a protective effect against clastogenicity of cyclosphosphamide (an alkylating drug) in mice. Using comet assay some in vivo studies have shown the antigenotoxic effects of dietary agents, namely, artepillin C (a polyphenolic acid found in Brazilian green propolis and Baccharis dracunculifolia) (Azevedo Bentes Monteiro Neto et al., 2011), safranal, (a constituent of Crocus sativus L. stigmas) (Hosseinzadeh and Sadeghnia, 2007), orange juice (Franke *et al.*, 2005b) and vitamin C (Franke *et al.*, 2005a) against DNA damage induced by methyl methanesulfonate (MMS). Also lemongrass protected leukocytes from DNA damage induced by N-methyl-N-nitrosurea (MNU) (Bidinotto *et al.*, 2010). Data from application of comet assay in the assessment of genoprotective effects of diet against alkylating DNA damage is limited. First, AlkA is, as far as we know, the only repair enzyme used for detection of alkylating DNA damage by the comet assay (Collins *et al.*, 2001a). Alk A recognises 3-MeA in DNA, but its specificity is low, detecting other modified bases, some of which are also other alkylated bases. Furthermore, 3-MeA is not the most abundant alkylating damage and it does not represent the alkylating damage with more mutagenic/carcinogenic potential. Other alkylating lesions, like N7MeG, the most abundant

lesion, and O6MeG, the most mutagenic, are until now undectectable by comet assay.

have investigated whether DNA repair activity can be modified by diet in humans.

DNA damage can arrest cell cycle progression to allow DNA repair, preventing, therefore, replication of errors, or to induce apoptosis to eliminate cells severely damaged. Defective DNA repair is usually linked to human cancer development. Therefore, enhancement of DNA repair can be understood as a prevention strategy against cancer and an important molecular target for dietary phytochemicals (Davis and Milner, 2007). However, few studies

New modifications of the comet assay have been developed to assess effects of dietary agents on DNA repair ability (as described above). Briefly, the "cellular repair assay"

**6.3 Effect of diet on induction of DNA repair** 

mice, respectively.

Recently, we reported that luteolin and luteolin-7-glucoside increased rejoining of strand breaks after treatment with H2O2 in Caco-2 cells. Luteolin-7-glucoside also had a BER inductive effect increasing incision activity in Caco-2 cells (Ramos *et al.*, 2010a; Ramos *et al.*, 2010b). Quercetin also increased rejoining of strand breaks induced by *t*-BHP in HepG2 (Ramos et al., 2008). Moreover, dietary agents such as flavonoids, vitamins E and C had been reported as inducers of oxidative DNA damage repair activity (Davis and Milner, 2007).
