Effects of administration of natural vitamin E on spontaneous hepatocarcinogenesis and N-nitrosodiethylamine initiated tumors in mice.

Nitta, Yumiko; Kamiya, Kenji; Tanimoto, Masanori; Kagimoto, Osamu; Niwa, Ohtsura; Yokoro, Kenjiro

doi:10.1293/tox.4.55

Cited by 9 publications

(6 citation statements)

References 9 publications

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“…However, p-carotene, vitamin A and vitamin E generate reactive oxygen species through the oxidation process, leading to oxidative DNA damage (11,12). Indeed, an excess amount of these antioxidants elevates cancer incidence (13)(14)(15). Although this study does not exclude the possibilities of actions as antioxidant or sunscreen by X A N derivatives, these results have shown that X A N derivatives act as effective quencher and protect from photosensitized D N A damage.…”

Section: Discussionmentioning

confidence: 99%

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Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage

Hirakawa¹,

Yoshida²,

Nagatsu³

et al. 2005

Photochem Photobiol

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Photosensitized DNA damage participates in solar-UV carcinogenesis, photogenotoxicity and phototoxicity. A chemoprevention of photosensitized DNA damage is one of the most important methods for the above phototoxic effects. In this study, the chemopreventive action of xanthone (XAN) derivatives (bellidifolin [BEL], gentiacaulein [GEN], norswertianin [NOR] and swerchirin [SWE]) on DNA damage photosensitized by riboflavin was demonstrated using [32P]-5'-end-labeled DNA fragments obtained from genes relevant to human cancer. GEN and NOR effectively inhibited the formation of piperidine-labile products at consecutive G residues by photoexcited riboflavin, whereas BEL and SWE did not show significant inhibition of DNA damage. The four XAN derivatives decrease the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidative product of G, by photoexcited riboflavin. The preventive action for the 8-oxodGuo formation of these XAN derivatives increased in the following order: GEN>NOR>>BEL>SWE. A fluorescence spectroscopic study and ab initio molecular orbital calculations suggested that the prevention of DNA photodamage is because of the quenching of the triplet excited state of riboflavin by XAN derivatives through electron transfer. This chemoprevention is based on neither antioxidation nor a physical sunscreen effect; rather, it is based on the quenching of a photosensitizer. In conclusion, XAN derivatives, especially GEN, may act as novel chemopreventive agents by the quenching mechanism of an excited photosensitizer.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, an excess amount of these antioxidants elevates cancer incidence (13)(14)(15). A physical sunscreen does not show a side effect but cannot effectively protect from the phototoxicity induced by visible light.…”

Section: Introductionmentioning

confidence: 99%

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage

Hirakawa¹,

Yoshida²,

Nagatsu³

et al. 2005

Photochem Photobiol

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“…However, β‐carotene, vitamin A and vitamin E generate reactive oxygen species through the oxidation process, leading to oxidative DNA damage (11,12). Indeed, an excess amount of these antioxidants elevates cancer incidence (13–15). Although this study does not exclude the possibilities of actions as antioxidant or sunscreen by XAN derivatives, these results have shown that XAN derivatives act as effective quencher and protect from photosensitized DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage^¶

Hirakawa

Yoshida

Nagatsu

et al. 2005

Photochem & Photobiology

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Photosensitized DNA damage participates in solar‐UV carcinogenesis, photogenotoxicity and phototoxicity. A chemoprevention of photosensitized DNA damage is one of the most important methods for the above phototoxic effects. In this study, the chemopreventive action of xanthone (XAN) derivatives (bellidifolin [BEL], gentiacaulein [GEN], norswertianin [NOR] and swerchirin [SWE]) on DNA damage photosensitized by riboflavin was demonstrated using [32P]‐5′‐end‐labeled DNA fragments obtained from genes relevant to human cancer. GEN and NOR effectively inhibited the formation of piperidine‐labile products at consecutive G residues by photoexcited riboflavin, whereas BEL and SWE did not show significant inhibition of DNA damage. The four XAN derivatives decrease the formation of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodGuo), an oxidative product of G, by photoexcited riboflavin. The preventive action for the 8‐oxodGuo formation of these XAN derivatives increased in the following order: GEN > NOR ≫ BEL > SWE. A fluorescence spectroscopic study and ab initio molecular orbital calculations suggested that the prevention of DNA photodamage is because of the quenching of the triplet excited state of riboflavin by XAN derivatives through electron transfer. This chemoprevention is based on neither antioxidation nor a physical sunscreen effect; rather, it is based on the quenching of a photosensitizer. In conclusion, XAN derivatives, especially GEN, may act as novel chemopreventive agents by the quenching mechanism of an excited photosensitizer.

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“…However, a recent epidemiological investigation in Finland failed to confirm this hypothesis: the incidence of lung cancer in male smokers was unaffected by α-tocopherol supplementation and was unexpectedly increased by β-carotene supplementation (). Several studies employing laboratory animals have also demonstrated that vitamin E can induce or promote tumor formation ( − ). Additionally, the present study showed that α-tocopherol induced oxidative DNA damage in the presence of Cu(II), although it was in a simplified, in vitro model.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, however, it has been suggested that, in the presence of Cu(II) ions (and in the absence of preformed hydroperoxides), the pro-oxidant properties of vitamin E can be accounted for by the formation of hydroxyl radicals ( • OH), generated following the interaction of Cu(I) with hydrogen peroxide (H 2 O 2 ) (). Since • OH is capable of reacting with all biomolecules at essentially diffusion-controlled rates, formation of the radical and its reaction with DNA following the interaction of α-tocopherol with copper ions may also be responsible for the reported tumorigenic properties of the vitamin ( − ). Indeed, Cu(II) ions are known to bind tightly to DNA, where they can interact with reducing agents (ascorbic acid, glutathione, phenolics, or NADH) and H 2 O 2 (which may be generated in situ from molecular oxygen), resulting in oxidative damage to the nucleic acid, including base modification and strand breakage ( − ).…”

Section: Introductionmentioning

confidence: 99%

α-Tocopherol Induces Oxidative Damage to DNA in the Presence of Copper(II) Ions

Yamashita

Murata

Inoue

et al. 1998

Chem. Res. Toxicol.

107

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There is currently much interest in the possibility that dietary antioxidants may confer protection from certain diseases, such as atherosclerosis and cancer. The importance of alpha-tocopherol (vitamin E) as a biological antioxidant is widely recognized. However, pro-oxidant properties of alpha-tocopherol have been observed in chemical systems, and it has been reported that the vitamin can induce tumor formation and act as a complete tumor promotor in laboratory animals. In the present communication, we find that alpha-tocopherol can act as a potent DNA-damaging agent in the presence of copper(II) ions, using a simplified, in vitro model. alpha-Tocopherol was found to promote copper-dependent reactive oxygen species formation from molecular oxygen, resulting in DNA base oxidation and backbone cleavage. Neither alpha-tocopherol nor Cu(II) alone induced DNA damage. Bathocuproine, a Cu(I)-specific chelator, and catalase inhibited the DNA damage, whereas free hydroxyl radical scavengers did not. The order of DNA cleavage sites was thymine, cytosine > guanine residues. Examinations using an oxygen electrode and cytochrome c indicate that molecular oxygen was consumed in the reaction of alpha-tocopherol and Cu(II) and that superoxide was formed. Stoichiometry studies showed that two Cu(II) ions could be reduced by each alpha-tocopherol molecule. Electron spin resonance spin-trapping investigations were then used to demonstrate that hydrogen peroxide interacts with Cu(I) to generate the reactive species responsible for DNA damage, which is either the hydroxyl radical or a species of similar reactivity. These findings may be of relevance to the tumorigenic properties of the vitamin reported in the literature. However, further studies are required to establish the significance of these reactions under in vivo conditions.

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Effects of administration of natural vitamin E on spontaneous hepatocarcinogenesis and N-nitrosodiethylamine initiated tumors in mice.

Cited by 9 publications

References 9 publications

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage^¶

α-Tocopherol Induces Oxidative Damage to DNA in the Presence of Copper(II) Ions

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Effects of administration of natural vitamin E on spontaneous hepatocarcinogenesis and N-nitrosodiethylamine initiated tumors in mice.

Cited by 9 publications

References 9 publications

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage

Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage¶

α-Tocopherol Induces Oxidative Damage to DNA in the Presence of Copper(II) Ions

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Chemopreventive Action of Xanthone Derivatives on Photosensitized DNA Damage^¶