Diet, life-style habits and malondialdehyde-deoxyguanosine adducts in a group of subjects resident in the rayong province, Thailand

Most human cancers result from environmental exposures and gene-environment interactions. Diet is an important component of lifestyle and its role in the maintenance of good health and as a determinant of different kind of chronic diseases, including cancer, has been extensively analyzed. Diet can contribute to cancer risk through the consumption of food mutagens, including those generated by cooking. On the other hand, diet that emphasizes the consumption of whole grain foods, legumes, vegetables and fresh fruit and that limit animal fat has been associated with decreased cancer risk. Indeed, a general protective effect against cancers at different sites has been reported for a number of fresh fruit and vegetables. In particular, fresh fruit is a food rich of phytochemicals that can act against reactive oxygen species (ROS) formation and induce the expression of DNA repair systems. Among life-style habits, tobacco cigarette smoking is an established cancer risk factor. In addition to be a relevant source of mutagens, tobacco smoke is also a major source of oxidative stress and ROS, capable to cause oxidative DNA damage. ROS can also induce lipid peroxidation (LPO), whose by-products can lead to endogenous DNA damage formation. MDA is a natural product of LPO, also formed during prostaglandins (PGH2) biosynthesis via cyclooxygenase (COX-1 and COX-2). MDA is an aldehyde capable to interact with cellular constituents including DNA, inducing the formation of M1dG adducts. The reaction with deoxyguanosine (dG) origins the formation of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one, e.g. the M1dG adducts. In addition to LPO and PGH2 biosynthesis, the formation of M1dG adducts can be induced by ROS through the production of base propenal intermediates. M1dG adducts have been shown to block the replication of DNA and induce base pair and frameshift mutations. Moreover, increased levels of M1dG adducts have been found in number of cancer patients. Higher amount of M1dG adducts have been also associated to worst surviving in lung cancer patients. Thus, the analysis of M1dG adduct formation is considered a promising biomarker that can reflect the whole oxidant status of an organism. In the present study, we have investigated the relationship between tobacco smoking, the consumption of fresh fruit and the formation of M1dG adducts in a group of people resident in Map Ta Phut (MTP), Rayong province, Thailand, including 53 residents in the Map Ta Phut Industrial Estate (MIE) area, and 46 individuals living in a control district of the same province without industrial exposures. The DNA adduct analysis was performed using the 32P-DNA postlabelling assay (Munnia et al., 2006). The potential involvement of the polymorphism of glutathione S-transferase Mu-1 (GSTM1) in the formation of endogenous DNA adducts has been also evaluated. Our findings indicate a statistically significant effect of tobacco smoke on M1dG formation (p <0.05). The increased intake of fresh fruit was inversely associated to the M1dG adduct production (p <0.05). Then, the GSTM1 polymorphism was not associated with the formation of M1dG adducts. Our data indicate that tobacco smoking habits can induce an enhanced formation of M1dG adducts, possibly through the production of ROS and LPO. Conversely, the consumption of fresh fruits was associated to a decreased formation of DNA damage. The increased formation of M1dG adducts in current smokers can be related to an excess of LPO induced from tobacco smoke constituents, as well from ROS produced during carcinogen metabolism. The protective effects of fresh fruit on M1dG adduct production may act on different biological mechanisms, for example by the induction of enzymes involved in DNA repair and by antioxidant effects. The GSTM1 polymorphism could be not relevant for the frequency of M1dG adducts.