Role of Oxidative DNA Damage in Dietary Carcinogenesis

Abstract

Dietary factors are implicated in approximately 35% of cancers attributed to environmental factors. Although an extremely wide variety of dietary factors are considered to contribute to carcinogenesis, its precise mechanism remains to be clariˆed. We focused on the role of oxidative DNA damage in carcinogenesis mediated by various dietary factors. We investigated the mechanism of oxidative DNA damage induced by a) amino acid metabolites, in relation to carcinogenesis caused by protein intake and amino acid imbalance, b) heterocyclic amines formed during cooking meat andˆsh, c) sugar and hyperglycemiarelated aldehydes, d) carcinogens contained in fermented foods, such as urethane, e) phytoestrogens including soy iso‰avones, f) carcinogens in edible plants, such as caŠeic acid and isothiocyanate, g) food additives, such as potassium bromate and benzoyl peroxide. These dietary factors and their metabolites induced metal-mediated oxidative damage to DNA in human cultured cells and 32 P-labeled DNA fragments obtained from human cancer-relevant genes. On the basis of our results, it is concluded that polycyclic compounds, such as heterocyclic amines, can cause oxidative DNA damage, although they appear to mainly form DNA adduct. On the other hand, monocyclic and aliphatic compounds, such as amino acid metabolites and urethane, may mainly cause oxidative DNA damage whereas they do not appear to form DNA adduct. Soy iso‰avones may cause carcinogenesis through initiation via oxidative DNA damage caused by their metabolites and promotion via cell proliferation induced by themselves. In this review, we discuss the role of oxidative DNA damage as the common mechanism of dietary carcinogenesis.

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“…Reactive oxygen species (ROS), such as superoxide anion (O2 -) and hydrogen peroxide (H2O2), are produced as normal byproducts of cellular metabolism (1). In the presence of transition metal ions, H 2 O 2 is quickly converted to a more powerful oxidant hydroxyl radical (･OH) via the Fenton reaction (2).…”

Mutagenicity of secondary oxidation products of 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate (8-hydroxy-2′- deoxyguanosine 5′-triphosphate)

“…Reactive oxygen species, such as superoxide, hydrogen peroxide, hydroxyl radical, and singlet oxygen, are produced through normal cellular metabolism, and by various environmental mutagens and dietary factors [1][2][3][4].…”

Suppression of mutagenesis by 8-hydroxy-2′-deoxyguanosine 5′-triphosphate (7,8-dihydro-8-oxo-2′-deoxyguanosine 5′-triphosphate) by human MTH1, MTH2, and NUDT5

“…The formation of ROS leads to the oxidation of cellular components and disturbs their normal functions. The formation of oxidized DNA lesions is one of the causative factors of mutagenesis, carcinogenesis, neurodegeneration, and aging [1][2][3][4][5].…”