N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA

Oikawa, Shinji; Yamada, Keitaro; Yamashita, Naruto; Tada‐Oikawa, Saeko; Kawanishi, Shosuke

doi:10.1093/carcin/20.8.1485

Cited by 96 publications

(55 citation statements)

References 46 publications

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“…Similarly, it was reported, using a simplified in vitro model, that an antioxidant vitamin E (␣-tocopherol) can act as a potent oxidative DNA-damaging agent in the presence of Cu(II) (14). Virtually all putative chemopreventive antioxidants may have potential carcinogenicity (18,20).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have revealed prooxidant effects of vitamin E (13,14) and vitamin C (15)(16)(17) under certain circumstances. Other antioxidants such as N-acetylcysteine (18) and quercetin (19,20) can cause oxidative damage to cellular and isolated DNA. ␤-Carotene may also act as both an antioxidant and a prooxidant under various oxygen partial pressures (21)(22)(23).…”

mentioning

confidence: 99%

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Oxidative DNA Damage by Vitamin A and Its Derivative via Superoxide Generation

Murata

Kawanishi²

2000

Journal of Biological Chemistry

174

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Recent intervention studies revealed that ␤-carotene supplement to smokers resulted in a higher incidence of lung cancer. However, the causal mechanisms remain to be clarified. We reported here that vitamin A (retinol) and its derivative (retinal) caused cellular DNA cleavage detected by pulsed field gel electrophoresis. Retinol and retinal significantly induced 8-oxo-7,8-dihydro-2-deoxyguanosine formation in HL-60 cells but not in H 2 O 2 -resistant HP100 cells, suggesting the involvement of H 2 O 2 in cellular DNA damage. Experiments using 32 P-labeled isolated DNA demonstrated that retinol and retinal caused Cu(II)-mediated DNA damage, which was inhibited by catalase. UV-visible spectroscopic and electron spin resonance-trapping studies revealed the generation of superoxide and carbon-centered radicals, respectively. The superoxide generation during autoxidation of retinoids was significantly correlated with the formation of 8-oxo-7,8-dihydro-2-deoxyguanosine, although the yield of carbon-centered radicals was not necessarily related to the intensity of DNA damage. These findings suggest that superoxide generated by autoxidation of retinoids was dismutated to H 2 O 2 , which was responsible for DNA damage in the presence of endogenous metals. Retinol and retinal have prooxidant abilities, which might lead to carcinogenesis of the supplements of ␤-carotene.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Oxidative DNA Damage by Vitamin A and Its Derivative via Superoxide Generation

Murata

Kawanishi²

2000

Journal of Biological Chemistry

174

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“…glutathione, which was an even more potent scavenger of free radicals than NAC itself [12]. On the other hand, NAC and other reducing agents were also shown to increase the oxidative DNA damages, depending on the experimental conditions, such as the presence or absence of transition metal ions [20,[33][34][35]. It was demonstrated that NAC treatment increased the extent of oxidative DNA damage when copper or iron ions were involved [18,20,36,37].…”

Section: The Effect Of N-acetyl-l L-cysteine On Dna Damagementioning

confidence: 99%

“…However, there are still considerable controversies regarding the antioxidant efficacy of NAC. Some published experimental results suggested that NAC could increase the oxidative damage to DNA [18][19][20]. For example, Devasagayam et al [21] found that the degradation of pBR322 by free radicals was enhanced by treatment with NAC.…”

Section: Introductionmentioning

confidence: 99%

Quantitative measurement of hydroxyl radical induced DNA double‐strand breaks and the effect of N‐acetyl‐l‐cysteine

Yang

2006

FEBS Letters

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Reactive oxygen species, such as hydroxyl or superoxide radicals, can be generated by exogenous agents as well as from normal cellular metabolism. Those radicals are known to induce various lesions in DNA, including strand breaks and base modifications. These lesions have been implicated in a variety of diseases such as cancer, arteriosclerosis, arthritis, neurodegenerative disorders and others. To assess these oxidative DNA damages and to evaluate the effects of the antioxidant N-acetyl-L L-cysteine (NAC), atomic force microscopy (AFM) was used to image DNA molecules exposed to hydroxyl radicals generated via Fenton chemistry. AFM images showed that the circular DNA molecules became linear after incubation with hydroxyl radicals, indicating the development of double-strand breaks. The occurrence of the double-strand breaks was found to depend on the concentration of the hydroxyl radicals and the duration of the reaction. Under the conditions of the experiments, NAC was found to exacerbate the free radical-induced DNA damage.

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“…Previous literatures have demonstrated that antioxidants can act as prooxidants under some circumstances [19]. It is found that b-carotene [20], vitamin E [21], quercetin [22], N-acetylcysteine [23] , and caffeic acid [24] can act as potent DNA damaging agents. Also, a potential clastogenic effect of known antioxidant compounds has been reported by others.…”

Section: Discussionmentioning

confidence: 99%

Cytogenetical and histochemical studies on curcumin in male rats

Makawy¹,

Sharaf²

2006

WIT Transactions on Biomedicine and Health, Vol 10

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Curcumin is a major component of the curcuma species, commonly used as a yellow coloring and flavoring agent in foods. Curcumin has been demonstrated to have potent antioxidant, anti-inflammatory activity and has shown anticancer properties in many rodent models. There is the perception that since compounds are natural, they are devoid of toxicity and safe to use. Some of the active compounds in supplements have inherent toxicity. In this study, five doses (0.5, 5, 10, 25 and 50 mg/kg/daily) of curcumin spice were orally administered to male rats daily for four weeks. The effect of curcumin was studied genetically by evaluation of chromosomal aberrations and micronucleus formation in bone marrow cells of male rats. Histopathological and histochemical investigations were studied in different tissues (liver, kidney) of males. The cytogenetical results showed that curcumin caused a statistically significant dose-dependent increase in the number of micronucleated polychromatic erythrocytes (MNPCEs) and in the frequencies of total chromosomal aberrations over the control. Also, results showed that there were significant differences between positive control and all curcumin-tested doses, except the dose of 50 mg/kg showed no significant difference. Histopathological results showed different degrees of alterations, as manifested by vacuolar degeneration in hepatocytes, tubular degeneration in renal tissues. We conclude that over use of curcumin spice may cause genotoxical and histopathological effects.

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N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA

Cited by 96 publications

References 46 publications

Oxidative DNA Damage by Vitamin A and Its Derivative via Superoxide Generation

Oxidative DNA Damage by Vitamin A and Its Derivative via Superoxide Generation

Quantitative measurement of hydroxyl radical induced DNA double‐strand breaks and the effect of N‐acetyl‐l‐cysteine

Cytogenetical and histochemical studies on curcumin in male rats

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