The Influence of Antioxidants on Cigarette Smoke-Induced DNA Single-Strand Breaks in Mouse Organs: A Preliminary Study with the Alkaline Single Cell Gel Electrophoresis Assay

Tsuda, Shuji; Matsusaka, Naonori; Ueno, Shunji; Susa, Nobuyuki; Sasaki, Yu

doi:10.1093/toxsci/54.1.104

Cited by 53 publications

(32 citation statements)

References 24 publications

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“…EA is a phenolic lactone that exerts its anticarcinogenic and antimutagenic activities through several mechanisms, including scavenging reactive oxygen species (30,57,58). This observation is in agreement with previous studies investigating the antioxidant activities of EA on DNA strand breaks (59,60). Our data suggest that CSC-induced DNA strand breaks may, in part, originate from free radicals.…”

Section: Discussionsupporting

confidence: 92%

“…Based upon our findings, we speculate that there may be two possible explanations for the lack of attenuation of basal levels of DNA strand breaks. First, cigarette smoke contains more than 5,000 chemicals with diverse interactions (60), which may influence the effectiveness of EA to act as an antioxidant. Second, in our laboratory, it has been reported that EA was a potent inhibitor of dibenzo[a,l]pyrene-DNA adducts in a microsome-mediated test system by ≥75% (61).…”

Section: Discussionmentioning

confidence: 99%

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Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells

Moktar

Ravoori²,

Vadhanam³

et al. 2009

Int J Oncol

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Abstract. Human papillomavirus (HPV) is the causative factor in the development and progression of cervical cancers in >97% of the cases, although insufficient. Epidemiological studies suggest an elevated risk of cervical cancer for cigarette smokers; therefore, we examined cigarette smoke-induced DNA damage and repair in HPV16-transformed human ectocervical cells (ECT1/E6 E7). Cells were treated with cigarette smoke condensate (CSC) for 72 h to assess the formation of single-and double-strand DNA breaks, measured by alkaline and neutral single cell gel electrophoresis assays, respectively. The mean tail length of cells with single-strand breaks was increased by 1.8-, 2.7-and 3.7-fold (p<0.001) after treatment with 4, 8 and 12 μg/ml CSC, respectively. The tail length with double-strand breaks was also increased dose-dependently. These results were further supported by measurement of the mean tail moment: the increase in both single-and double-strand breaks were much more pronounced with increasing concentration of CSC, by up to 23.5-fold (p<0.0001 for both assays). To examine the DNA repair, cells were treated with CSC for 72 h, followed by CSC withdrawal and re-incubation of the cells with fresh medium for 24, 48, or 72 h. Both single-and double-strand DNA breaks were removed during the initial 24 h but no further removal of the damage was observed. Up to 80% of residual single-and double-strand DNA breaks (p<0.05) were found to persist at all CSC concentrations examined. Ellagic acid, a known antioxidant and free-radical scavenger, was found to significantly inhibit DNA breaks induced by CSC. Thus, free radicals may be a plausible source of CSCinduced DNA damage. These data show that CSC-mediated DNA strand breaks are highly persistent, and suggest that persistence of cigarette smoke-associated DNA damage in the presence of HPV infection may lead to increased mutations in cervical cells and ultimately higher cancer risk.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells

Moktar

Ravoori²,

Vadhanam³

et al. 2009

Int J Oncol

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“…In general, CS leads to apoptosis by means of oxidative stress, mitochondrial and nuclear damage, and TNF receptor signaling (Tsuda et al, 2000;Carnevali et al, 2003;Tuder et al, 2003). CS-induced single strand DNA break by acute CS exposure is caused by stimulation of free radicals (Tsuda et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin-1 Ameliorates Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Sato

Hoshino²,

Hara³

et al. 2008

J Pharmacol Exp Ther

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Cigarette smoking is associated with the development of inflammatory lung diseases representing major health problems worldwide. We hypothesized that the redox-regulating molecule thioredoxin-1 (TRX), which shows anti-inflammatory, antioxidative, and antiapoptotic effects, could be induced by cigarette smoke (CS) and contribute to protect against CS-induced inflammation and lung destruction. In an acute study, human TRX transgenic mice and C57BL6/J mice were exposed to mainstream CS for 3 days. In the lungs of CS-exposed mice, bronchial epithelial injury and bronchoalveolar lavage neutrophilia were observed. Oxidative stress and apoptosis were enhanced, and the expression of cytokines macrophage inflammatory protein-2 and tumor necrosis factor (TNF)-␣ was increased 15.3-and 2.4-fold, respectively. Compared with C57BL6/J mice, TRX-transgenic mice had significantly less inflammation, oxidative damage, and apoptosis, as well as decreased levels of matrix metalloprotease-12 mRNA and serum TNF-␣. When recombinant human TRX (40 g/body/day, 3 days) was injected i.p. into CS-exposed C57BL6/J mice, a significant effect to offer protection against CS-induced lung injury was observed through suppression of neutrophil influx. In the chronic study, TRXtransgenic mice and C57BL6/J mice were exposed to CS for 6 months. This chronic exposure caused pulmonary emphysema in C57BL6/J mice accompanying prominent infiltration of macrophages and neutrophils to lung. These pathological changes were significantly suppressed in TRX-transgenic mice. In conclusion, TRX induction ameliorated CS-induced lung inflammation and emphysema in mice. TRX-1 may therefore play a preventive or therapeutic role in lung inflammatory disorders such as chronic obstructive pulmonary disease.Cigarette smoke (CS)-associated diseases such as ischemic heart disease, diabetes mellitus, and pulmonary diseases are the major health problem. Among those, the most important is chronic obstructive pulmonary disease (COPD) because morbidity is high and increasing (Pauwels et al., 2001;Rabe et al., 2007). The pathology of COPD is characterized as inflammation of the airways and loss of alveolar structure. The development of COPD is associated with chronic smoking that cause chronic inflammation, oxidative stress, and proteolysis. CS induces the production of large numbers of reactive oxygen species (ROS), which disturb the balance between oxidants and antioxidants, promoting lung cell apoptosis and amplifying the inflammatory responses in the lungs (Rabe et al., 2007).The activation of alveolar macrophage by oxidants results in releasing of several inflammatory cytokines and chemotactic factors that recruit circulating inflammatory cells such as neutrophils, which are also a secondary source of ROS (Hautamaki et al., 1997;Ofulue et al., 1998). TNF-␣ is a well documented chemotactic factor that is activated by the macrophage metalloelastase MMP-12 in a CS-induced lung inflammation (Churg et al., 2003). The recruited neutrophils and activated alveolar macrophages...

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“…However, the time between last exposure and dissection might have been too long. It has been reported, although under rather different smoke exposure conditions (1-min exposure and extremely high smoke concentration), that the level of DNA strand breaks in the lung returns to control values already after 1 hour (69). In vitro, cigarette smoke is clearly active (70).…”

Section: Discussionmentioning

confidence: 96%

“…Both studies found a positive effect, however, despite the high smoke concentrations (dilution around 1/7, in our study 1/100), the short daily exposure times (10 min and 1 min, respectively) resulted in lower daily inhalation doses (time × concentration). Theoretical doses were 75% and 10%, respectively (73,69); however, it can be assumed that the actual doses were significantly lower, as rodents, if briefly exposed, are known to lower their respiratory minute volume drastically as a function of the irritative potency of the inhalant (74). A further explanation for the failure of the Comet assay to show smoke-related responses in our study could be the cross-linking effect of aldehydes in smoke, which can inhibit DNA migration preventing the detection of increases in strand breaks in the assay (72,75).…”

Section: Discussionmentioning

confidence: 99%

Cigarette-Smoke- and Age-Dependent Oxidative Stress Effects in Rats

Meisgen

Roemer

Conroy

et al. 2014

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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SUMMARYOxidative stress is a basic mechanism involved in both ageand smoking-related diseases. To test whether smoking affects young, old, and calorie-restricted organisms to the same extent, we assessed oxidative stress parameters in the lung, heart, and liver of male Fischer 344 rats (4 months old and 19-22 months old) exposed to air or cigarette mainstream smoke. Smoke-related effects were seen for parameters of DNA damage, lipid peroxidation, protein oxidation, and glycoxidation. No smoke-related effects were observed for DNA damage in the lung and heart (Comet assay) and for malondialdehyde in the lung. The old rats showed higher smoke-related responses than the young rats for 8-hydroxy-desoxyguanosine (8-OHdG) in the heart and liver, DNA damage in the liver, and protein carbonyls in the lung; however, there was little evidence for an overadditive effect of smoking on aging. Caloric restriction, which is known to retard aging effects, also had little impact on smoke-related oxidative changes. [Beitr. Tabakforsch. Int. 26 (2014) 109-120]

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The Influence of Antioxidants on Cigarette Smoke-Induced DNA Single-Strand Breaks in Mouse Organs: A Preliminary Study with the Alkaline Single Cell Gel Electrophoresis Assay

Cited by 53 publications

References 24 publications

Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells

Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells

Thioredoxin-1 Ameliorates Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Cigarette-Smoke- and Age-Dependent Oxidative Stress Effects in Rats

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