DNA Damage Protection and Induction of Repair by Dietary Phytochemicals and Cancer Prevention: What Do We Know?

Abstract

DNA damage accumulates in cells over time as a result of exposure to a variety of exogenous and endogenous agents. These damages, if not repaired properly, can generate mutations in somatic or germline cells, which are involved in the pathogenesis of many diseases, such as cancer. To maintain genomic integrity generation after generation, organisms possess multiple mechanisms such as inhibition of carcinogen uptake into the cells, induction of detoxification enzymes, increased cellular defenses that prevent DNA damage, enhancement of DNA repair, increased anti-inflammatory activity, inhibition of cell proliferation, and modulation of apoptosis through effects on signal transduction pathways (de Kok et al., 2008); (Pan et al., 2008). In the last decades, several dietary constituents have been shown to modulate all these processes. Epidemiological studies as well as laboratory data suggest that consumption of fruits and vegetables is associated with a reduced risk of developing a wide range of cancers. It has been estimated that 3040% of all tumours can be prevented with a correct lifestyle and diet, in particular colon cancer (Rajamanickam and Agarwal, 2008). Multiple mechanisms have been proposed to explain the chemopreventive effects of phytochemicals. Protection of DNA from damage and modulation of DNA repair assume an important role on prevention of mutations and consequently of the carcinogenic process. The comet assay or single cell gel electrophoresis (SCGE) assay is a rapid, sensitive and relatively simple method for assessing DNA damage and its repair in individual cells. The standard comet assay measures DNA breaks and alkali-labile sites that are converted to strand breaks. With its widespread use, several modifications on the comet assay have been made that allow the quantification of other types of DNA damage as well as DNA repair rates. With the inclusion of an extra step on the comet assay by using specific DNA repair enzymes, different base lesions can be identified by the introduction of breaks at sites of base damage. In this regard, Endonuclease III, FPG and AlkA have been used to detect oxidized pyrimidines, modified purines and alkylpurines bases, respectively. With these