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Journal ArticleDOI

Reduction in oxidatively generated DNA damage following smoking cessation.

TL;DR: Results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term.
Abstract: Background Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.

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Journal ArticleDOI
TL;DR: Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD), which is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians.
Abstract: Background Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians. Methods A systematic review of published studies on the association between smoking and increased risk for AD and preclinical and human literature on the relationships between smoking, nicotine exposure, and AD-related neuropathology was conducted. Original data from comparisons of smoking and never-smoking cognitively normal elders on in vivo amyloid imaging are also presented. Results Overall, literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD. Conclusions A reduction in the incidence of smoking will likely reduce the future prevalence of AD.

284 citations


Additional excerpts

  • ...[182] Box HC, O’Connor RJ, Patrzyc HB, Iijima H, Dawidzik JB,...

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Journal ArticleDOI
TL;DR: The continuing development and improvement of LC-MS/MS coupled with the stable isotope-dilution method for DNA adduct quantification will further promote research about the clinical implications and diagnostic applications of oxidatively induced DNAAdducts.
Abstract: A variety of endogenous and exogenous agents can induce DNA damage and lead to genomic instability. Reactive oxygen species (ROS), an important class of DNA damaging agents, are constantly generated in cells as a consequence of endogenous metabolism, infection/inflammation, and/or exposure to environmental toxicants. A wide array of DNA lesions can be induced by ROS directly, including single-nucleobase lesions, tandem lesions, and hypochlorous acid (HOCl)/hypobromous acid (HOBr)-derived DNA adducts. ROS can also lead to lipid peroxidation, whose byproducts can also react with DNA to produce exocyclic DNA lesions. A combination of bioanalytical chemistry, synthetic organic chemistry, and molecular biology approaches have provided significant insights into the occurrence, repair, and biological consequences of oxidatively induced DNA lesions. The involvement of these lesions in the etiology of human diseases and aging was also investigated in the past several decades, suggesting that the oxidatively induce...

124 citations

Journal ArticleDOI
TL;DR: It is indicated that smoking of hand-rolled cigarettes has stronger genotoxic and oxidative effects on the metabolism than smoking of manufactured filter-cigarettes, and it is proposed that these harmful effects could be attributed to the higher level of oxidants.
Abstract: Cigarette smoking is a major cause of human cancer at various sites, although its carcinogenic mechanisms still remain unestablished. Based on the use of a filter, cigarette smoke can be divided into a gas phase and a tar phase. Both contain different concentrations of oxidants, free radicals and tobacco-specific carcinogens. To explore the effects of both filtered and non-filtered cigarette smoke on DNA damage and oxidative status, we measured the level of mononuclear leukocyte DNA damage by use of the single-cell gel electrophoresis (Comet) assay. We also determined malondialdehyde (MDA), protein carbonyl content (PC) and total antioxidative capacity (TAC) levels in blood plasma of smokers of manufactured filter-cigarettes and of hand-rolled cigarettes. Cotinine levels were also measured in plasma to estimate the degree of smoking. Mononuclear leukocyte DNA damage, plasma MDA, plasma PC and plasma cotinine levels were found significantly higher, while plasma TAC levels were found significantly lower in smokers of filter-cigarettes and smokers of hand-rolled cigarettes, compared with control subjects. TAC levels in hand-rolled and manufactured filter-cigarette smokers were not significantly different from each other. However, the levels of DNA damage, plasma MDA, plasma cotinine, and plasma protein oxidation were significantly higher in hand-rolled cigarette smokers than in filter-cigarette smokers. There was a significant positive correlation between MDA and DNA damage in both hand-rolled cigarette smokers and manufactured filter-cigarette smokers. This study indicates that smoking of hand-rolled cigarettes has stronger genotoxic and oxidative effects on the metabolism than smoking of manufactured filter-cigarettes. We propose that these harmful effects could be attributed to the higher level of oxidants.

27 citations

Journal ArticleDOI
TL;DR: Increasing age, male gender, smoking history, and sTNF-RI levels were associated with short LTL among persons with BE but no correlations were observed between LTL and other inflammatory markers or measures of obesity.
Abstract: Telomere shortening is associated with increasing age, male gender and lifestyle factors such as obesity and smoking. Inflammation has also been implicated in cellular senescence and may promote telomere shortening in chronic conditions such as obesity and diabetes. However, little is known about the relationship between markers of obesity and inflammation, and leukocyte telomere length (LTL). LTL was measured using quantitative polymerase chain reaction in peripheral leukocytes from 295 individuals diagnosed with Barrett’s esophagus (BE) between 1995 and 2009. Data on lifestyle variables including obesity and smoking were collected at in-person interviews. Biomarkers of obesity (leptin, adiponectin), diabetes (glucose, insulin), inflammation (C-reactive protein, Interleukin-6, surface tumor necrosis factor receptor (sTNFR) I & II) and oxidative stress (F2-isoprostanes) were measured in stored blood samples. We examined associations between these covariates and LTL in a cross-sectional analysis using linear and logistic regression models, adjusting for possible confounders. LTL was significantly associated with age (r = −0.30, p < 0.001), gender (r = 0.14 for females, p = 0.01) and inversely associated with cigarette pack-years (r = −0.11, p = 0.04). Odds of having short LTL were significantly higher for participants in the highest tertile for sTNF-RI (Odds ratio adjusted for age, gender, smoking, and obesity = 2.19; 95 % CI 1.00–4.85, p-trend = 0.02). LTL was not significantly associated with any other lifestyle factors, including smoking or obesity, or other inflammation-, obesity-/diabetes-related biomarkers measured. Increasing age, male gender, smoking history, and sTNF-RI levels were associated with short LTL among persons with BE but no correlations were observed between LTL and other inflammatory markers or measures of obesity. Larger longitudinal studies are necessary in order to further establish the potential relationships between obesity, inflammation markers and LTL.

18 citations


Cites methods from "Reduction in oxidatively generated ..."

  • ...For every variable of interest, three different models were run: unadjusted, age- and gender-adjusted, and further adjusted for smoking and obesity, both major correlates of inflammation [29, 30]....

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Journal ArticleDOI
TL;DR: An inverse association between smoking behaviour during pregnancy and birth length was observed, with shortest length in active smokers followed by passive smoking mothers, and the observed increase in umbilical cord serum levels of vitamins A and E may subserve antioxidative processes in response to tobacco smoke-induced oxidative stress.
Abstract: Smoking during pregnancy has been shown to be detrimental for the developing fetus. The effects of active and passive maternal smoking on umbilical cord serum levels of vitamin A and vitamin E were examined. Secondary measures included anthropometric parameters in the newborn. Maternal and umbilical cord serum levels of vitamins A and E were measured at delivery. The mothers were assigned to three groups: non-smoking (n 12); passive smoking (n 13); active smoking (n 18). Based on multivariate linear regressions, active smoking during pregnancy was associated with increased umbilical cord serum levels of vitamin A and vitamin E. While enhanced circulating levels of vitamin A in cord blood were also found in non-smoking mothers exposed to tobacco smoke during pregnancy, those of vitamin E were not influenced. Further, an inverse association between smoking behaviour during pregnancy and birth length was observed, with shortest length in active smokers followed by passive smoking mothers. Active and passive maternal smoking behaviour during pregnancy increases the fetal demand for antioxidant compounds in order to counteract the oxidative burden by cigarette smoke. Against this background, the observed increase in umbilical cord serum levels of vitamins A and E may subserve antioxidative processes in response to tobacco smoke-induced oxidative stress. This would reduce the availability of vitamins A and E for fetal maturation, which is critical inasmuch as both compounds are indispensable for the developing fetus. However, due to the cross-sectional nature of our observation, this line of reasoning definitely requires validation in cause-effect experiments in the future.

10 citations


Cites background from "Reduction in oxidatively generated ..."

  • ...These compounds have been shown to produce DNA damage((4)), which may contribute to the detrimental effects of maternal smoking on fetal development....

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References
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Journal ArticleDOI
TL;DR: In this paper, the persistence at various times (3, 7, 14, 21, 28, 42, and 56 days) of eight tobacco smoke carcinogen and toxicant biomarkers in the urine of 17 smokers who stopped smoking was determined.
Abstract: We determined the persistence at various times (3, 7, 14, 21, 28, 42, and 56 days) of eight tobacco smoke carcinogen and toxicant biomarkers in the urine of 17 smokers who stopped smoking. The biomarkers were 1-hydroxy-2-(N-acetylcysteinyl)-3-butene (1) and 1-(N-acetylcysteinyl)-2-hydroxy-3-butene (2) [collectively called MHBMA for monohydroxybutyl mercapturic acid] and 1,2-dihydroxy-4-(N-acetylcysteinyl)butane (3) [DHBMA for dihydroxybutyl mercapturic acid], metabolites of 1,3-butadiene; 1-(N-acetylcysteinyl)-propan-3-ol (4, HPMA for 3-hydroxypropyl mercapturic acid), a metabolite of acrolein; 2-(N-acetylcysteinyl)butan-4-ol (5, HBMA for 4-hydroxybut-2-yl mercapturic acid), a metabolite of crotonaldehyde; (N-acetylcysteinyl)benzene (6, SPMA for S-phenyl mercapturic acid), a metabolite of benzene; (N-acetylcysteinyl)ethanol (7, HEMA for 2-hydroxyethyl mercapturic acid), a metabolite of ethylene oxide; 1-hydroxypyrene (8) and its glucuronides (1-HOP), metabolites of pyrene; and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (9) and its glucuronides (total NNAL), a biomarker of exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These biomarkers represent some of the major carcinogens and toxicants in cigarette smoke: 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, polycyclic aromatic hydrocarbons (PAH), and NNK. With the exception of DHBMA, levels of which did not change after cessation of smoking, all other biomarkers decreased significantly after 3 days of cessation (P < 0.001). The decreases in MHBMA, HPMA, HBMA, SPMA, and HEMA were rapid, nearly reaching their ultimate levels (81-91% reduction) after 3 days. The decrease in total NNAL was gradual, reaching 92% after 42 days, while reduction in 1-HOP was variable among subjects to about 50% of baseline. Since DHBMA did not change upon smoking cessation, there appear to be sources of this metabolite other than 1,3-butadiene. The results of this study demonstrate that the tobacco smoke carcinogen/toxicant biomarkers MHBMA, HPMA, HBMA, SPMA, HEMA, 1-HOP, and NNAL are related to smoking and are good indicators of the impact of smoking on human exposure to 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, PAH, and NNK.

147 citations

Journal ArticleDOI
TL;DR: It is confirmed that certain oxidative damage biomarkers are elevated in smokers even after a period of abstinence from smoking, whereas these plus some others are elevated after acute smoking.

139 citations


"Reduction in oxidatively generated ..." refers background in this paper

  • ...Recent papers have used other approaches and markers of oxidative stress related to cigarette smoking in addition to d(G), including isoprostanes, hydroxyeicosatetraenoic acid products (HETEs), and advanced glycation end-products [27-29]....

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Journal Article
TL;DR: The results of this study demonstrate that the tobacco smoke carcinogen/toxicant biomarkers MHBMA, HPMA, HBMA, SPMA, HEMA, 1-HOP, and NNAL are related to smoking and are good indicators of the impact of smoking on human exposure to 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, polycyclic aromatic hydrocarbons (PAH), and NNK.
Abstract: Tobacco carcinogen and toxicant biomarkers, quantitative measurements of exposure and fate of specific tobacco carcinogens and toxicants, could in principle become an important part of a risk algorithm to identify smokers susceptible to lung cancer and are also important for the evaluation and potentially the regulation of new and existing tobacco products. Our goal is to develop a panel of tobacco carcinogen and toxicant biomarkers applicable in these activities. One validation criterion for a tobacco carcinogen or toxicant biomarker is its relationship to tobacco use. This can be determined by assessing the decrease in a biomarker level when people stop using the product. Therefore, in this study, we evaluated the relationship to cigarette smoking of eight tobacco carcinogen and toxicant biomarkers: 1-hydroxypyrene (1-HOP), a metabolite of pyrene and a widely accepted biomarker of exposure to carcinogenic polycyclic aromatic hydrocarbons; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), an established biomarker of exposure to the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 6 mercapturic acids (MA) derived from: 1,3 butadiene (MHBMA and DHBMA), acrolein (HPMA), crotonaldehyde (HBMA), benzene (SPMA), and ethylene oxide (HEMA) . Smokers provided 24h urine samples twice while still smoking and then on days 3, 7, 14, 21, 28, 42, and 56 after quitting. Seventeen subjects (11 female) completed the study. Their mean age (± S.D.) was 43.9 ± 11.0 years (range 23 - 58). Sixteen were Caucasian and one was of mixed racial heritage. They had been smoking an average of 17.3 ± 12.3 years and smoked 21.8 ± 6.7 cigarettes per day. MAs were quantified by a newly developed combined LC-negative ion-APCI-MS/MS method, total NNAL by GC-nitrosamine selective detection, and 1-HOP by LC-fluorescence. Baseline values of the biomarkers could be split into three groups: low, medium, and high. NNAL, 1-HOP, and SPMA comprised the low group (1-3 nmol/24h), HEMA and MHBMA the medium group (30 - 50 nmol/24h), and DHBMA, HPMA, and HBMA the high group (2600 - 11,000 nmol/24h). Levels of all MAs except DHBMA decreased rapidly after smoking cessation. In each case, the mean reduction of the MA from baseline was approximately 80% (P Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3014.

137 citations


"Reduction in oxidatively generated ..." refers background in this paper

  • ...Carmella and colleagues [25] proposed that sensitivity to changes in smoking (e....

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Journal ArticleDOI
TL;DR: Smoking cessation significantly reduces the urinary excretion rate of 8-oxodG, giving direct and controlled evidence that cigarette smoking causes an increased rate of oxidative DNA modification, which could represent a mechanism by which tobacco smoke is carcinogenic.
Abstract: BACKGROUND Reactive oxygen species from, e.g. tobacco smoke are suggested to be involved in carcinogenesis by oxidative modification of DNA. The urinary excretion rate of the oxidized nucleoside 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) has been validated as a biomarker of the rate of oxidative DNA modification with mechanistic relation to carcinogenesis. In cross-sectional studies, the urinary excretion rate of 8-oxodG has been shown to be elevated in smokers compared with non-smokers. PURPOSE In this randomised, controlled smoking cessation study, we investigated whether cigarette smoking per se causes oxidative DNA modification. METHODS Of the 182 healthy smokers included, 100 were randomized to quit smoking after baseline samples had been taken, and 82 were randomized to continue usual smoking. Before the start of the study and after 4 weeks, the subjects collected 24-h urine samples that were analysed for 8-oxodG content by high-pressure liquid chromatography with electrochemical detection. The subjects randomized to smoking cessation were followed up after 26 weeks. RESULTS Four weeks of smoking cessation resulted in a 21% decrease in 8-oxodG excretion rate (from mean +/- SD, 30.5 +/- 13.9 to 24.1 +/- 10.5 nmol/24 h, P < 0.001) in 58 quitters included in per-protocol data analysis. Sixty-five continued smokers included in per-protocol analysis showed a 9% decrease in 8-oxodG excretion rate (from 31.6 +/- 13.2 to 28.7 +/- 12.6 nmol/24 h, P = 0.026). After 4 weeks, the 8-oxodG excretion rate was 16% (95% confidence interval 4 to 28%) higher in the continued smokers than in the quitters (P = 0.0085, ANCOVA), demonstrating the effect of smoking per se. A 23% (P < 0.005) decrease in 8-oxodG excretion rate was sustained for 26 weeks in 27 quitters who completed the study. CONCLUSION Smoking cessation significantly reduces the urinary excretion rate of 8-oxodG, giving direct and controlled evidence that cigarette smoking causes an increased rate of oxidative DNA modification. This could represent a mechanism by which tobacco smoke is carcinogenic.

109 citations


"Reduction in oxidatively generated ..." refers background in this paper

  • ...Priemé and colleagues [12] reported a decrease of about 20% in d(G) among those quitting smoking up to 26 weeks....

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Journal Article
TL;DR: The biochemical evidence suggests that exposure to ETS causes oxidative stress, resulting in DNA damage that may increase the risk of certain diseases.
Abstract: Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Our objective was to determine the oxidative stress effects of ETS on employees who are exposed. The results provide information that is useful to the resolution of risk assessment questions associated with ETS. We analyzed two blood draws from volunteers in our control and exposed groups. The level of exposure to ETS was determined through plasma cotinine measurements, which showed a 65% increase from the control group to the exposed group. Exposure to ETS resulted in a statistically significant increase of 63% of the oxidative DNA mutagen 8-hydroxy-2'-deoxyguanosine in the blood of exposed subjects. This oxidative DNA damage has been linked to an increased risk of developing several degenerative chronic diseases, including coronary heart disease and cancer. The exposed subjects also had increased levels of superoxide dismutase, catalase, glutathione peroxidase (GPOX), and glutathione reductase. However, these increases were only statistically significant in catalase and GPOX. Catalase levels were 13% higher in the exposed group, and GPOX levels were 37% higher in exposed volunteers. The biochemical evidence suggests that exposure to ETS causes oxidative stress, resulting in DNA damage that may increase the risk of certain diseases.

103 citations


"Reduction in oxidatively generated ..." refers background in this paper

  • ...[17] showing elevated levels in those occupationally exposed to SHS....

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  • ...Indeed, other research has noted exposure to SHS as a potential source of oxidative damage in nonsmokers, [17,18] so this remains a plausible explanation....

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