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1.
J Clin Biochem Nutr ; 72(3): 242-247, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37251967

RESUMO

Second-hand smoke exposure is an established cause of several adverse health effects. Tobacco smoke exposure in the environment has been improved by the WHO Framework Convention on Tobacco Control. However, concerns have been raised regarding the health effects of heated tobacco products. Analysis of tobacco smoke biomarkers is critical for assessing the health effects of second-hand tobacco smoke exposure. In this study, nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine) and carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were analysed in the urine of non-smokers with or without passive exposure to cigarettes and heated tobacco products. In addition, 7-methylguanine and 8-hydroxy-2'-deoxyguanosine were simultaneously measured as DNA damage markers. The results revealed higher levels of urinary nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in participants exposed to second-hand tobacco smoke (both cigarettes and heated tobacco products) at home. In addition, the urinary levels of 7-methylguanine and 8-hydroxy-2'-deoxyguanosine tended to be higher in the second-hand tobacco smoke-exposed group. The urinary levels of nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were high in workplaces with no protection against passive smoking. These biomarkers will be useful for evaluating passive exposure to tobacco products.

2.
J Bone Miner Metab ; 40(6): 927-939, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36163519

RESUMO

INTRODUCTION: Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models. MATERIALS AND METHODS: Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor. RESULTS: The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway. CONCLUSIONS: This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Masculino , Camundongos , Suínos , Animais , Sarcopenia/patologia , Camundongos Endogâmicos C57BL , Qualidade de Vida , Pulmão , Estresse Oxidativo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Modelos Animais de Doenças , Elastase Pancreática/metabolismo , Músculo Esquelético/metabolismo
3.
BMC Public Health ; 22(1): 1098, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650608

RESUMO

BACKGROUND: Under the outbreak of Coronavirus disease 2019 (COVID-19), a structural equation model was established to determine the causality of important factors that affect Chinese citizens' COVID-19 prevention behavior. METHODS: The survey in Qingdao covered several communities in 10 districts and used the method of cluster random sampling. The research instrument used in this study is a self-compiled Chinese version of the questionnaire. Of the 1215 questionnaires, 1188 were included in our analysis. We use the rank sum test, which is a non-parametric test, to test the influence of citizens'basic sociodemographic variables on prevention behavior, and the rank correlation test to analyze the influencing factors of prevention behavior. IBM AMOS 24.0 was used for path analysis, including estimating regression coefficients and evaluating the statistical fits of the structural model, to further explore the causal relationships between variables. RESULTS: The result showed that the score in the prevention behavior of all citizens is a median of 5 and a quartile spacing of 0.31. The final structural equation model showed that the external support for fighting the epidemic, the demand level of health information, the cognition of (COVID-19) and the negative emotions after the outbreak had direct effects on the COVID-19 prevention behavior, and that negative emotions and information needs served as mediating variables. CONCLUSIONS: The study provided a basis for relevant departments to further adopt epidemic prevention and control strategies.


Assuntos
COVID-19 , Povo Asiático , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Cognição , Humanos , Inquéritos e Questionários
4.
J Clin Biochem Nutr ; 69(1): 37-43, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34376912

RESUMO

Concerns have recently grown about the health effects of secondhand smoke exposure and heated tobacco products. The analysis of tobacco smoke biomarkers is critical to assess the health effects of tobacco smoke exposure. For this purpose, the simultaneous determinations of exposure markers and health effect markers would provide a better evaluation of smoke exposure. In this study, nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in urine were analyzed as exposure markers. The DNA damage markers, 7-methylguanine and 8-hydroxy-2'-deoxyguanosine, were simultaneously measured as health effect markers. The results revealed significant levels of urinary nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in the subjects exposed to secondhand smoke and heated tobacco products. In addition, the urinary levels of 7-methylguanine and 8-hydroxy-2'-deoxyguanosine tended to be high for secondhand smoke and heated tobacco products exposures, as compared to those of non-smokers. These biomarkers will be useful for evaluating tobacco smoke exposure.

5.
J Clin Biochem Nutr ; 68(1): 18-22, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33536708

RESUMO

The urinary 8-hydroxy-2'-deoxyguanosine levels have been widely used as a biomarker of oxidative stress. The purpose of this study is to investigate the diurnal and day-to-day variations of urinary 8-hydroxy-2'-deoxyguanosine levels. For the diurnal variation, the urine samples were collected at the time of awakening and every 2 h, from 10:00 to 22:00, from 6 healthy participants. For the day-to-day variation, the urine samples were collected at the time of awakening for 35 consecutive days, from 27 healthy participants. As a result, no differences were observed in the diurnal urinary 8-hydroxy-2'-deoxyguanosine levels, and each subject had a characteristic 8-hydroxy-2'-deoxyguanosine level. On the other hand, the daily 8-hydroxy-2'-deoxyguanosine values showed a certain range of variation reflecting lifestyle factors, such as stress status, exercise, sleep time, drinking and diet. In conclusion, urinary 8-hydroxy-2'-deoxyguanosine may be a useful biomarker to control and prevent oxidative stress-related diseases, if the certain range of day-to-day variations of urinary 8-hydroxy-2'-deoxyguanosine is known. Even with only one measurement per year, the baseline urinary 8-hydroxy-2'-deoxyguanosine level could be achieved in a few years by incorporating the 8-hydroxy-2'-deoxyguanosine measurement as part of an annual health check. As the number of subjects was limited, further studies are needed for practical applications.

6.
J UOEH ; 41(4): 431-436, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31866661

RESUMO

Oxidative stress in biological components has become recognized as one of the causative factors of various diseases. In this study, we investigated the effects of worker lifestyle and fatigue on the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress. Our results revealed that urinary 8-OHdG level was increased by alcohol intake and decreased by snack intake and adequate sleep time on the day before the survey. A decrease in urinary 8-OHdG level was also observed in parallel with a decrease in workload. Urinary 8-OHdG monitoring is expected to be useful for disease prevention in the future.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/análogos & derivados , Estilo de Vida , Saúde Ocupacional , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina/urina , Biomarcadores/urina , Humanos
7.
Psychosom Med ; 80(1): 28-33, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28700458

RESUMO

OBJECTIVE: Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. METHODS: This cross-sectional study included 6517 individuals aged 45 to 74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector. RESULTS: Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one-category increase of stress; ptrend = .025), even after adjusting for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG. CONCLUSIONS: In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.


Assuntos
Dano ao DNA/fisiologia , Desoxiguanosina/análogos & derivados , Depressão/fisiopatologia , Estresse Oxidativo/fisiologia , Estresse Psicológico/fisiopatologia , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Estudos Transversais , Desoxiguanosina/urina , Depressão/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/urina
8.
J Clin Biochem Nutr ; 62(3): 238-241, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29892162

RESUMO

Nanoparticles are widely used as useful industrial materials. Therefore, their possible adverse health effects must be appraised. We assessed and compared the oxidative DNA damage caused by four different nanoparticles (TiO2, NiO, ZnO and CeO2). The effects of the administration methods, intratracheal instillation and inhalation, were also evaluated. Rats were subjected to intratracheal instillations or 4 weeks of inhalation exposure to the nanoparticles, and the 8-hydroxydeoxyguanosine (8-OHdG) levels in the lung were analyzed by an HPLC-EC detector method. The 8-OHdG levels were increased in a dose-dependent manner with the inhalation of NiO. ZnO also increased the 8-OHdG levels with inhalation. In comparison with the control, the 8-OHdG levels were significantly and persistently higher with the CeO2 nanoparticle administration, by both intratracheal instillation and inhalation. In contrast, there were no significant differences in the 8-OHdG levels between the control and TiO2 nanoparticle-treated groups, with either intratracheal instillation or inhalation during the observation period. These results indicated that NiO, ZnO and CeO2 nanoparticles generate significant amounts of free radicals, and oxidative stress may be responsible for the lung injury caused by these nanoparticles. In addition, both intratracheal instillation and inhalation exposure induced similar tendencies of oxidative DNA damage with these nanoparticles.

9.
Int J Mol Sci ; 18(12)2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29257061

RESUMO

The hazards of various types of nanoparticles with high functionality have not been fully assessed. We investigated the usefulness of biopersistence as a hazard indicator of nanoparticles by performing inhalation and intratracheal instillation studies and comparing the biopersistence of two nanoparticles with different toxicities: NiO and TiO2 nanoparticles with high and low toxicity among nanoparticles, respectively. In the 4-week inhalation studies, the average exposure concentrations were 0.32 and 1.65 mg/m³ for NiO, and 0.50 and 1.84 mg/m³ for TiO2. In the instillation studies, 0.2 and 1.0 mg of NiO nanoparticles and 0.2, 0.36, and 1.0 mg of TiO2 were dispersed in 0.4 mL water and instilled to rats. After the exposure, the lung burden in each of five rats was determined by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES) from 3 days to 3 months for inhalation studies and to 6 months for instillation studies. In both the inhalation and instillation studies, NiO nanoparticles persisted for longer in the lung compared with TiO2 nanoparticles, and the calculated biological half times (BHTs) of the NiO nanoparticles was longer than that of the TiO2 nanoparticles. Biopersistence also correlated with histopathological changes, inflammatory response, and other biomarkers in bronchoalveolar lavage fluid (BALF) after the exposure to nanoparticles. These results suggested that the biopersistence is a good indicator of the hazards of nanoparticles.


Assuntos
Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Traqueia/efeitos dos fármacos , Animais , Inalação , Instilação de Medicamentos , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Níquel/química , Ratos , Ratos Endogâmicos F344 , Titânio/química
10.
J Clin Biochem Nutr ; 61(1): 14-17, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28751804

RESUMO

Green tea ('Sencha'), made from the leaves of Camellia sinensis, is the most well-researched antioxidant beverage. The major source of its antioxidant activity is polyphenols, consisting mainly of catechins (flavan-3-ols). However, little is known about the physiological effects of green tea aroma, which lacks catechins. In the present study, we performed inhalation experiments with green tea aroma to evaluate its antioxidant activity in mice. As a result, the urinary 8-hydroxydeoxyguanosine levels were significantly decreased in comparison with those of the non-treated group, and the serum antioxidant capacity was significantly increased by the inhalation administration of green tea aroma. Furthermore, the increase in the urinary 8-hydroxydeoxyguanosine levels due to whole-body X-ray irradiation was significantly suppressed by the inhalation of green tea aroma. This is the first study to show the antioxidant activity of green tea aroma in vivo.

11.
Cancer Sci ; 107(11): 1653-1659, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27575995

RESUMO

Physical activity (PA) is recommended to both promote and maintain health and prevent cancer by improving the body's DNA repair system, which is considered a mechanism of cancer prevention. However, associations between PA and urinary levels of 8-hydroxydeoxyguanosine (8-OH-dG), which reflects DNA damage, are unclear. This cross-sectional study included 2370 men and 4052 women aged 45-74 years enrolled between 2010 and 2012. Habitual PA was assessed by single-axis accelerometer and urinary 8-OH-dG levels by automated HPLC. Multiple linear regression analysis was used to examine the relationship between log-transformed urinary 8-OH-dG and total PA (TPA) and PA of moderate/vigorous intensity (MVPA; ≥3 metabolic equivalents), with adjustment for age, body mass index, energy intake, alcohol consumption, smoking status, daily coffee drinking, menopause status (in women), and TPA (for MVPA). On multivariate adjustment, urinary 8-OH-dG levels were inversely correlated with TPA (ß = -0.020, P < 0.01) in women, and this correlation was not changed by PA intensity. Conversely, urinary 8-OH-dG levels were inversely correlated with MVPA (ß = -0.022, P < 0.05) in men, although the correlation with TPA was non-significant. This inverse correlation was clearer in current smokers than in never or former smokers, although the interaction between smoking status and MVPA on urinary 8-OH-dG levels was non-significant. In conclusion, greater TPA in women and greater MVPA in men were correlated with reduction in urinary 8-OH-dG, suggesting sex-specific effects of MVPA and TPA on protection from oxidative DNA damage. Increasing PA may mediate reduction in oxidative stress.


Assuntos
Desoxiguanosina/análogos & derivados , Exercício Físico/fisiologia , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Acelerometria , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Carcinogênese/metabolismo , Desoxiguanosina/urina , Ingestão de Energia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologia , Inquéritos e Questionários
12.
J UOEH ; 35(2): 119-27, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23774655

RESUMO

8-Hydroxydeoxyguanosine (8-OH-dG) is the most extensively analyzed oxidative stress marker. Recently, 8-hydroxyguanine (free base: 8-OH-Gua) has been recognized as an oxidative stress marker. To verify the usefulness of 8-OH-Gua, the 8-OH-dG and 8-OH-Gua levels in the urine and the 8-OH-Gua levels in the serum of type 2 diabetic model animals, db/db mice, were measured as oxidative stress markers by a column switching HPLC-system coupled to an electrochemical detector. The urinary 8-OH-Gua and 8-OH-dG levels in db/db mice (7-26 weeks old) were significantly higher than those in control (db/m+) mice. The 8-OH-Gua levels in the serum of the db/db mice were also about 2-fold higher than those in the control mice at 26 weeks of age. In addition, the urinary levels of 8-OH-dG and 8-OH-Gua increased with age (9-26 weeks). A significant positive correlation was obtained between the 8-OH-dG and 8-OH-Gua levels in urine. Although no difference was observed in the 8-OH-dG levels in the liver and kidney DNA between the diabetic and control mice, these results suggested that urinary 8-OH-dG and free base 8-OH-Gua in urine or serum may be good biomarkers of oxidative stress.


Assuntos
Envelhecimento/metabolismo , Biomarcadores/análise , Diabetes Mellitus Experimental/metabolismo , Guanina/análogos & derivados , Estresse Oxidativo/fisiologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Cromatografia Líquida de Alta Pressão , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Feminino , Guanina/análise , Guanina/sangue , Guanina/urina , Camundongos
13.
Nutrients ; 15(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37960186

RESUMO

The oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, was designed to assess a composite measure of multiple pro-oxidant and antioxidant effects on an individual's oxidative stress status. This study aimed to evaluate whether OBSs were inversely associated with urinary levels of 8-hydroxydeoxyguanosine (8-OHdG)-an oxidative stress marker-among Japanese adults. This cross-sectional study was based on data obtained during 2010-2012. Overall, 7552 participants from the J-MICC Study Saga who answered a self-administered food frequency questionnaire were recruited for the final analysis. OBSs were calculated from 11 pro-oxidant and antioxidant lifestyle factors, including dietary intake, physical activity, and alcohol and smoking status. Urinary 8-OHdG values were corrected by creatinine level (ng/mg creatinine). Our findings revealed a higher total OBS was significantly associated with lower urinary 8-OHdG/creatinine levels after adjustment for covariates in men and women (p for trend < 0.01 in both sexes). We performed a multiple regression analysis of the association between OBSs and urinary 8-OHdG/creatinine levels stratified by age, body mass index (BMI), and menopausal status and found consistent negative associations in most groups for both sexes. No significant differences in the 60-64 age group for women (standardized ß = -0.09, p = 0.13) or BMI < 18.5 kg/m2 for men (standardized ß = -0.18, p = 0.17) were observed. A higher OBS had a strong inverse association with urinary 8-OHdG/creatinine levels in men and women among Japanese adults. The OBS might be a useful tool for evaluating the roles of oxidative stress-related lifestyle factors, including diet.


Assuntos
Desoxiguanosina , População do Leste Asiático , Masculino , Humanos , Adulto , Feminino , 8-Hidroxi-2'-Desoxiguanosina , Espécies Reativas de Oxigênio , Estudos Transversais , Creatinina , Antioxidantes/metabolismo , Estresse Oxidativo , Biomarcadores/urina
14.
J Occup Health ; 63(1): e12210, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33689200

RESUMO

OBJECTIVE: Oxidative stress is considered to cause lifestyle-related diseases, including cancer. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is widely analyzed as an oxidative stress marker. We extensively scrutinized the relationships between 8-OHdG levels and lifestyle choices as carcinogenic factors. METHODS: In this study, we investigated health examination results and working conditions affecting urinary 8-OHdG levels in 503 male workers. RESULTS: The urinary 8-OHdG level was positively associated with high blood sugar and leanness in smokers. In addition, urinary 8-OHdG tended to increase with organic solvent or hydrochloric acid exposure, as well as long working hours. On the other hand, the urinary 8-OHdG level was negatively associated with high plasma LDL-cholesterol levels in non-smokers and anemia. CONCLUSION: According to the results, anemia decreased the oxidative stress, regardless of smoking status, while leanness or high blood sugar increased the oxidative stress in smokers, and the presence of plasma cholesterol contributed to the lower oxidative stress in non-smokers. Certain types of occupational exposure may cause oxidative stress. The measurement of urinary 8-OHdG at annual health checks may be a useful biomarker for preventing lifestyle- and work-related diseases.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/urina , Biomarcadores/urina , Exposição Ocupacional/análise , Saúde Ocupacional/estatística & dados numéricos , Exame Físico/estatística & dados numéricos , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Local de Trabalho , Adulto Jovem
15.
Chem Res Toxicol ; 23(3): 630-6, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-20055452

RESUMO

4-Oxo-2-hexenal (4-OHE), which forms a 2'-deoxyguanosine (dG) adduct in a model lipid peroxidation system, is mutagenic in the Ames test. It is generated by the oxidation of omega-3 fatty acids and is commonly found in dietary fats, such as fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts with 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), and 5-methyl-2'-deoxycytidine (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts in detail. We measured the amounts of 4-OHE-DNA adducts in mouse organs by LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE-dA, 4-OHE-dC, 4-OHE-dG, and 4-OHE-5-Me-dC adducts were detected in stomach and intestinal DNA in the range of 0.25-43.71/10(8) bases. After the 4-OHE administration, the amounts of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE-dC in human lung DNA, in the range of 2.6-5.9/10(9) bases. No difference in the 4-OHE adduct levels was detected between smokers and nonsmokers. Our results suggest that 4-OHE-DNA adducts are formed by endogenous as well as environmental lipid peroxides.


Assuntos
Aldeídos/efeitos adversos , Adutos de DNA/análise , Adutos de DNA/metabolismo , Mutagênicos/efeitos adversos , Animais , Bovinos , DNA/metabolismo , Adutos de DNA/química , Feminino , Humanos , Peroxidação de Lipídeos , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Conformação de Ácido Nucleico
16.
Bioorg Med Chem Lett ; 20(1): 260-5, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19914833

RESUMO

In this Letter, we demonstrate the formation of m(5)dC from dC or in DNA by dimethylsulfoxide (DMSO) and methionine sulfoxide (MetO), under physiological conditions in the presence of the Fenton reagent in vitro. DMSO reportedly affects the cellular epigenetic profile, and enhances the metastatic potential of cultured epithelial cells. The methionine sulfoxide reductase (Msr) gene was suggested to be a metastatis suppressor gene, and the accumulation of MetO in proteins may induce metastatic cancer. Our findings are compatible with these biological data and support the hypothesis that chemical cytosine methylation via methyl radicals is one of the mechanisms of DNA hypermethylation during carcinogenesis. In addition to m(5)dC, the formation of 8-methyldeoxyguanosine (m(8)dG) was also detected in DNA under the same reaction conditions. The m(8)dG level in human DNA may be a useful indicator of DNA methylation by radical mechanisms.


Assuntos
Metilação de DNA , DNA/metabolismo , Dimetil Sulfóxido/química , Radical Hidroxila/química , Metionina/análogos & derivados , Cromatografia Líquida de Alta Pressão , DNA/genética , Epigênese Genética , Humanos , Peróxido de Hidrogênio/química , Ferro/química , Metionina/química , Espectrometria de Massas em Tandem
17.
Genes Environ ; 42: 26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944094

RESUMO

INTRODUCTION: Urinary nicotine and cotinine levels are often measured as biomarkers for tobacco smoke exposure. However, these biomarkers are not appropriate to evaluate the effects of quitting smoking for several days, because of their short half-lives. In this study, we focused on the changes in the urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels of 55 patients in a smoking cessation program, because of the long half-life. At the same time, urinary 7-methylguanine (m7Gua) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as DNA damage markers of cigarette smoking, were also measured. RESULTS: In the subjects who completed the quit-smoking program (18 subjects out of 55), the urinary nicotine and cotinine levels decreased to 1.7 and 0.2% at 8 weeks after the first visit to the clinic. By contrast, the NNAL levels decreased to 12.3% at 8 weeks after quitting smoking. During the same period, the urinary m7Gua levels significantly decreased, from 27.32 µg/mg creatinine to 14.17 µg/mg creatinine by the elimination of subjects who showed increased levels of NNAL during the smoking cessation program. The 8-OHdG levels were also reduced within the same period, but were not significantly different. From the all data analysis, the urinary levels of cotinine and NNAL positively correlated with the level of m7Gua. CONCLUSIONS: NNAL may be an appropriate exposure marker for evaluating the smoking status of patients in a smoking cessation program. The urinary cotinine and NNAL levels positively correlated with the m7Gua levels.

18.
PLoS One ; 14(2): e0212499, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30768632

RESUMO

BACKGROUND: It remains unclear whether daily physical activity is associated with DNA damage. This cross-sectional study examined the association between leisure-time physical activity and urinary 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of oxidative DNA damage, or urinary 7-methylguanine (m7Gua), a biomarker of methylating DNA damage. METHODS: Participants included 501 workers (294 men and 207 women), aged 20-65 years, from municipal offices in Japan. Urinary 8-OH-dG and m7Gua were measured using column-switching HPLC. Physical activity was evaluated using a self-reported questionnaire. The associations between leisure-time physical activity and urinary DNA damage markers were assessed by multiple linear regression analysis, with stratification by occupational physical activity. RESULTS: After adjusting for covariates, leisure-time physical activity showed a suggestive inverse correlation with urinary 8-OH-dG levels (P for trend = 0.06), and a significant inverse association with urinary m7Gua levels (P for trend = 0.03). In analysis stratified by occupation, inverse correlations were observed in sedentary workers (walking < 30 min/day at work: P for trend = 0.06 and = 0.03 for urinary 8-OH-dG and m7Gua, respectively), but not in physically active workers (walking ≥ 30 min/day at work). In analysis for each intensity of leisure-time physical activity, light-intensity exercise was associated with lower levels of urinary 8-OH-dG (P for trend = 0.03), whereas moderate-to-high-intensity exercise was associated with lower levels of urinary m7Gua (P for trend = 0.02). CONCLUSIONS: Our results suggest that high levels of leisure-time physical activity are associated with decreased levels of DNA damage in individuals with low physical activity at work.


Assuntos
Dano ao DNA , Exercício Físico , Atividades de Lazer , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Povo Asiático , Biomarcadores/urina , Estudos Transversais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Guanina/análogos & derivados , Guanina/urina , Humanos , Japão , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Ocupações , Adulto Jovem
19.
J Radiat Res ; 60(5): 573-578, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31251351

RESUMO

Clinical radiodiagnosis and radiotherapy sometimes induce tissue damage and/or increase the risk of cancer in patients. However, in radiodiagnosis, a reduction in the exposure dose causes a blockier image that is not acceptable for diagnosis. Approximately 70% of DNA damage is induced via reactive oxygen species and/or radicals created during X-ray irradiation. Therefore, treatment with anti-oxidants and/or radical scavengers is considered to be effective in achieving a good balance between image quality and damage. However, few studies have examined the effect of using radical scavengers to reduce radiation damage in the clinical setting. In this study, we administrated 20 mg/kg ascorbic acid (AA) to patients before cardiac catheterization (CC) for diagnostic purposes. We analyzed changes in the number of phosphorylated H2AX (γH2AX) foci (a marker of DNA double-strand breaks) in lymphocytes, red blood cell glutathione levels, blood cell counts, and biochemical parameters. Unfortunately, we did not find satisfactory evidence to show that AA treatment reduces γH2AX foci formation immediately after CC. AA treatment did, however, cause a higher reduced/oxidized glutathione ratio than in the control arm immediately after CC. This is a preliminary study, but this result suggests that reducing radiation damage in clinical practice can be achieved using a biological approach.


Assuntos
Ácido Ascórbico/farmacologia , Cateterismo Cardíaco , Ácido Ascórbico/sangue , Eritrócitos/metabolismo , Glutationa/sangue , Histonas/metabolismo , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Fosforilação , Projetos Piloto
20.
Nutrition ; 47: 63-68, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29429538

RESUMO

OBJECTIVE: The aim of this study was to investigate the potential links between dietary non-enzymatic antioxidant capacity (NEAC) in overall diet and separately from foods and beverages and markers of DNA damage. METHODS: The participants were 513 employees, 20 to 65 y of age. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG) and 7-methylguanine (m7 Gua) were measured using column-switching high-performance liquid chromatography. Dietary NEAC was determined from databases of NEAC measurements obtained by different assays: ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). Dietary NEAC for each participant was calculated by multiplying the estimated NEAC values with the consumed amount and summing up those values, which was ascertained by a validated brief self-administered diet history questionnaire. Multiple-regression analyses were performed to assess the associations between dietary NEAC and 8-OHdG and m7 Gua, with adjustment for potential confounders. RESULTS: No statistically significant associations were found between overall dietary NEAC or NEAC from either foods or beverages and urinary 8-OHdG levels, after adjustment for potential confounders (overall: FRAP, Ptrend = 0.40; ORAC, P = 0.27; TRAP, P = 0.45). Likewise, no association was found between overall dietary NEAC and m7 Gua levels (FRAP, Ptrend = 0.30; ORAC, P = 0.65; TRAP, P = 0.41). However, we did identify significant inverse association between NEAC from foods, as estimated by TRAP, and m7 Gua levels (Ptrend = 0.049). CONCLUSION: Overall, dietary NEAC was not associated with 8-OHdG or m7 Gua levels. In contrast, dietary NEAC from foods but not beverages may be inversely associated with DNA damage caused by methylation.


Assuntos
Antioxidantes/análise , Dano ao DNA , Dieta/estatística & dados numéricos , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Guanina/análogos & derivados , Guanina/urina , Humanos , Masculino , Pessoa de Meia-Idade , Capacidade de Absorbância de Radicais de Oxigênio , Fatores de Risco , Adulto Jovem
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