Publications by authors named "Yun-Shan Li"

25 Publications

  • Page 1 of 1

Urinary biomarkers for secondhand smoke and heated tobacco products exposure.

J Clin Biochem Nutr 2021 Jul 9;69(1):37-43. Epub 2021 Mar 9.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

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, -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.
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http://dx.doi.org/10.3164/jcbn.20-183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325761PMC
July 2021

Health examination results and work environment factors affecting urinary 8-hydroxy-2'-deoxyguanosine levels.

J Occup Health 2021 Jan;63(1):e12210

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health Japan, Kitakyushu, Japan.

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.
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http://dx.doi.org/10.1002/1348-9585.12210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945954PMC
January 2021

Diurnal and day-to-day variation of urinary oxidative stress marker 8-hydroxy-2'-deoxyguanosine.

J Clin Biochem Nutr 2021 Jan 10;68(1):18-22. Epub 2020 Jul 10.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.

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.
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http://dx.doi.org/10.3164/jcbn.19-105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844656PMC
January 2021

Effects of smoking cessation on biological monitoring markers in urine.

Genes Environ 2020 11;42:26. Epub 2020 Sep 11.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555 Japan.

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 (mGua) 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 mGua 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 mGua.

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 mGua levels.
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http://dx.doi.org/10.1186/s41021-020-00165-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488543PMC
September 2020

[Workers' Lifestyles and Urinary 8-hydroxydeoxyguanosine as an Oxidative Stress Marker].

J UOEH 2019 ;41(4):431-436

Department of Environmental Oncology Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan.

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.
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http://dx.doi.org/10.7888/juoeh.41.431DOI Listing
August 2020

Pilot clinical study of ascorbic acid treatment in cardiac catheterization.

J Radiat Res 2019 Oct;60(5):573-578

Department of Radiological Health Science, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1093/jrr/rrz038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805981PMC
October 2019

Leisure-time physical activity and DNA damage among Japanese workers.

PLoS One 2019 15;14(2):e0212499. Epub 2019 Feb 15.

Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212499PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377137PMC
November 2019

Oxidative DNA damage in the rat lung induced by intratracheal instillation and inhalation of nanoparticles.

J Clin Biochem Nutr 2018 May 7;62(3):238-241. Epub 2018 Feb 7.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

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 (TiO, NiO, ZnO and CeO). 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 CeO nanoparticle administration, by both intratracheal instillation and inhalation. In contrast, there were no significant differences in the 8-OHdG levels between the control and TiO nanoparticle-treated groups, with either intratracheal instillation or inhalation during the observation period. These results indicated that NiO, ZnO and CeO 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.
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http://dx.doi.org/10.3164/jcbn.17-70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990410PMC
May 2018

Measurement of 8-hydroxyguanine as an oxidative stress biomarker in saliva by HPLC-ECD.

Genes Environ 2018 4;40. Epub 2018 Apr 4.

2Department of Health Development, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555 Japan.

Introduction: Oxidative stress leads to many kinds of diseases. Currently, urinary 8-hydroxydeoxyguanosine (8-OHdG) is widely measured as an oxidative stress biomarker. There is a specific advantage if saliva can be used as the sample to measure the oxidative stress biomarker, because saliva is much easier to collect than urine. In this study, we investigated the measurement of 8-hydroxyguanine (8-OHGua) as an oxidative stress marker in saliva, by a column switching HPLC system equipped with an electrochemical detector (HPLC-ECD).

Findings: The 8-OHGua in saliva could be detected as a single peak by HPLC-ECD. The average level of 8-OHGua in saliva was 3.80 ng/mL in ordinary, non-smoking subjects. The salivary 8-OHGua levels of smokers were significantly higher than those of non-smokers.

Conclusions: Salivary 8-OHGua may be a useful noninvasive and promising oxidative stress biomarker.
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http://dx.doi.org/10.1186/s41021-018-0095-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883350PMC
April 2018

Dietary non-enzymatic antioxidant capacity and DNA damage in a working population.

Nutrition 2018 03 4;47:63-68. Epub 2018 Jan 4.

Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.

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 (m 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 m 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, P = 0.40; ORAC, P = 0.27; TRAP, P = 0.45). Likewise, no association was found between overall dietary NEAC and m Gua levels (FRAP, P = 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 m Gua levels (P = 0.049).

Conclusion: Overall, dietary NEAC was not associated with 8-OHdG or m Gua levels. In contrast, dietary NEAC from foods but not beverages may be inversely associated with DNA damage caused by methylation.
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http://dx.doi.org/10.1016/j.nut.2017.10.004DOI Listing
March 2018

Biopersistence of NiO and TiO₂ Nanoparticles Following Intratracheal Instillation and Inhalation.

Int J Mol Sci 2017 Dec 19;18(12). Epub 2017 Dec 19.

Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.

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.
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http://dx.doi.org/10.3390/ijms18122757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751356PMC
December 2017

Comparison of Blueberry ( spp.) and Vitamin C via Antioxidative and Epigenetic Effects in Human.

J Cancer Prev 2017 Sep 30;22(3):174-181. Epub 2017 Sep 30.

Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul, Korea.

Background: Chemopreventive effects and the underlying mechanisms of blueberry ( spp.) are not clearly understood in human. We hypothesized blueberry would work via antioxidative and epigenetic modulation, which is similar to vitamin C.

Methods: We performed a pilot and non-inferiority study in healthy young women (n = 12), who consumed vitamin C (1 g/d) or 240 mL of blueberry juice (total polyphenols 300 mg and proanthocyanidin 76 mg/d) for 2 weeks. We analyzed 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels in their urine, and global and specific DNA methylation at the NAD(P)H quinone oxidoreductase 1 (), methylenetetrahydrofolate reductase (), or DNA methyltransferase 1 () genes in their blood.

Results: Urinary 8-OHdG levels were reduced by blueberry consumption rather than by vitamin C. The methylation (%) of the was significantly decreased in blueberry-consumers and the antioxidant-susceptible subgroup, whose urinary MDA levels were decreased by the intervention. We also found a positive correlation between changes of urinary 8-OHdG and of DNA methylation at the or the ( < 0.05). However, the genetic polymorphism of the (C677T in exon 4) did not affect any above markers.

Conclusions: Blueberry juice shows similar anti-oxidative or anti-premutagenic activity to vitamin C and the potential as a methylation inhibitor for the and the in human.
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http://dx.doi.org/10.15430/JCP.2017.22.3.174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624458PMC
September 2017

Antioxidant properties of green tea aroma in mice.

J Clin Biochem Nutr 2017 Jul 15;61(1):14-17. Epub 2017 Jun 15.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

Green tea ('Sencha'), made from the leaves of , 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 .
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http://dx.doi.org/10.3164/jcbn.16-80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525016PMC
July 2017

Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage.

Psychosom Med 2018 01;80(1):28-33

From the Department of Preventive Medicine (Shimanoe, Hara, Nishida, Horita, Tanaka), Faculty of Medicine, Saga University, Saga; Department of Public Health (Nanri), Showa University School of Medicine; Department of Nutritional Science (Yamada), National Institute of Health and Nutrition, Tokyo; Department of Environmental Oncology (Li, Kasai, Kawai), Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu; and Laboratory of Exercise Physiology (Higaki), Faculty of Sports and Health Science, Fukuoka University, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1097/PSY.0000000000000513DOI Listing
January 2018

Intensity-specific effect of physical activity on urinary levels of 8-hydroxydeoxyguanosine in middle-aged Japanese.

Cancer Sci 2016 Nov;107(11):1653-1659

Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.

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 (β = -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 (β = -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.
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http://dx.doi.org/10.1111/cas.13070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132284PMC
November 2016

Urinary 1-hydroxypyrene and 8-hydroxydeoxyguanosine levels among coke-oven workers for 2 consecutive days.

J Occup Health 2014 4;56(3):178-85. Epub 2014 Mar 4.

Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health.

Objectives: This study evaluated the levels of exposure to polycyclic aromatic hydrocarbons (PAHs) and their relationship with oxidative DNA damage among Vietnamese coke-oven workers.

Methods: We collected urine from 36 coke-oven workers (exposed group) at the beginning and end of the shift on 2 consecutive days. We also collected urine from 78 medical staff (control group). Information was collected by questionnaire about smoking status, drinking habit, and working position. Urinary 1-hydroxypyrene (1-OHP) and 8-hydroxydeoxyguanosine (8-OH-dG) were measured using HPLC. All statistical analyses were performed with SPSS version 19.

Results: Urinary 1-OHP was significantly higher in the coke-oven workers than in the control group (p<0.05). Top-oven workers had the highest levels of internal exposure to PAHs, followed by side-oven and then bottom-oven workers (5.41, 4.41 and 1.35 ng/mg creatinine, respectively, at the end of the shift on day 2). Urinary 8-OH-dG was significantly higher in top- and side-oven workers at the end of the shift on day 2 (4.63 and 5.88 ng/mg creatinine, respectively) than in the control group (3.85 ng/mg creatinine). Based on a multi-regression analysis, smoking status had a significant effect on urinary 8-OH-dG (p=0.049). Urinary 1-OHP tended to have a positive correlation with urinary 8-OH-dG (p=0.070).

Conclusions: Vietnamese coke-oven workers were exposed to PAHs during their work shift. Urinary 1-OHP exceeded the recommended limit, and elevated oxidative DNA damage occurred in top- and side-oven workers on the second day of work. A tendency for positive correlation was found between urinary 1-OHP and urinary 8-OH-dG.
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http://dx.doi.org/10.1539/joh.13-0222-oaDOI Listing
August 2015

8-hydroxyguanine in urine and serum as an oxidative stress marker: effects of diabetes and aging.

J UOEH 2013 Jun;35(2):119-27

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan.

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.
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http://dx.doi.org/10.7888/juoeh.35.119DOI Listing
June 2013

Free radical-mediated cytosine C-5 methylation triggers epigenetic changes during carcinogenesis.

Biomol Concepts 2013 Jun;4(3):213-20

The methylation of the C-5 position of deoxycytidine (dC) in the promoter regions of tumor suppressor genes is often observed in cancer cells. We found that various environmental agents, as well as endogenous compounds such as methionine sulfoxide (MetO), generate methyl radicals and modify dC to form 5-methyl-dC in DNA in vitro. We confirmed that both DNA methylation and cancer incidence in the liver were increased by the administration of MetO to oxidatively stressed mice. In this review, we summarize previous reports on methyl radical generation in vitro and in vivo and DNA modifications by methyl radicals, including our discoveries, as well as our recent experimental evidence suggesting that free radical-mediated dC methylation triggers epigenetic changes.
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http://dx.doi.org/10.1515/bmc-2012-0052DOI Listing
June 2013

Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine.

Antioxid Redox Signal 2013 Jun 31;18(18):2377-91. Epub 2013 Jan 31.

Department of Occupational and Environmental Medicine, University of Gothenburg, Gothenburg, Sweden.

Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability.

Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (rp 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples).

Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker.

Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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http://dx.doi.org/10.1089/ars.2012.4714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671631PMC
June 2013

Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice.

J Clin Biochem Nutr 2012 May 10;50(3):211-6. Epub 2012 Feb 10.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

Several mechanisms regarding the adverse health effects of nanomaterials have been proposed. Among them, oxidative stress is considered to be one of the most important. Many in vitro studies have shown that nanoparticles generate reactive oxygen species, deplete endogenous antioxidants, alter mitochondrial function and produce oxidative damage in DNA. 8-Hydroxy-2'-deoxyguanosine is a major type of oxidative DNA damage, and is often analyzed as a marker of oxidative stress in human and animal studies. In this study, we focused on the in vivo toxicity of metal oxide and silver nanoparticles. In particular, we analyzed the induction of micronucleated reticulocyte formation and oxidative stress in mice treated with nanoparticles (CuO, Fe(3)O(4), Fe(2)O(3), TiO(2), Ag). For the micronucleus assay, peripheral blood was collected from the tail at 0, 24, 48 and 72 h after an i.p. injection of nanoparticles. Following the administration of nanoparticles by i.p. injection to mice, the urinary 8-hydroxy-2'-deoxyguanosine levels were analyzed by the HPLC-ECD method, to monitor the oxidative stress. The levels of 8-hydroxy-2'-deoxyguanosine in liver DNA were also measured. The results showed increases in the reticulocyte micronuclei formation in all nanoparticle-treated groups and in the urinary 8-hydroxy-2'-deoxyguanosine levels. The 8-hydroxy-2'-deoxyguanosine levels in the liver DNA of the CuO-treated group increased in a dose-dependent manner. In conclusion, the metal nanoparticles caused genotoxicity, and oxidative stress may be responsible for the toxicity of these metal nanoparticles.
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http://dx.doi.org/10.3164/jcbn.11-70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334374PMC
May 2012

Exposure to polycyclic aromatic hydrocarbons, arsenic and environmental tobacco smoke, nutrient intake, and oxidative stress in Japanese preschool children.

Sci Total Environ 2011 Jul 12;409(15):2881-7. Epub 2011 May 12.

Department of Environmental Studies, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8563, Japan.

The association between oxidative stress and exposure to environmental chemicals was assessed in a group of Japanese preschool children. The concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 1-hydroxypyrene (1-OHP), inorganic arsenic (iAs) and monomethylarsonic acid (MMA), and cotinine in spot urine samples, collected from 134 children (3-6 yrs) from a kindergarten in Kanagawa, Japan, were measured as biomarkers of oxidative stress or exposure to environmental chemicals. For 76 subjects of the 134, intakes of anti-oxidant nutrients (vitamins A, C, and E, manganese, copper, zinc and selenium (Se)) were estimated from a food consumption survey carried out 2-4 weeks after urine sampling and by urine analysis (Se). The median (min-max) creatinine-corrected concentrations of urinary biomarkers were 4.45 (1.98-12.3), 0.127 (0.04-2.41), 4.78 (1.18-12.7), and 0.62 (<0.6-19.0) μg/g cre for 8-OHdG, 1-OHP, iAs+MMA, and cotinine, respectively. Multiple regression analysis was carried out using 8-OHdG concentration as a dependent variable and urinary biomarkers of exposure and Se intake, intakes of vitamins and biological attributes of the subjects as independent variables. To explain 8-OHdG concentrations, intake of vitamin A and age were significant variables with negative coefficients, while 1-OHP concentration had a positive coefficient. These results indicated that oxidative stress of children is affected by chemical exposure at environmental levels, by nutrient intake and by physiological factors in a complex manner. On the other hand, unstable statistical results due to sub-grouping of subject, based on the availability of food consumption data, were found: the present results should further be validated by future studies with suitable research design.
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http://dx.doi.org/10.1016/j.scitotenv.2011.04.028DOI Listing
July 2011

DNA modifications by the omega-3 lipid peroxidation-derived mutagen 4-oxo-2-hexenal in vitro and their analysis in mouse and human DNA.

Chem Res Toxicol 2010 Mar;23(3):630-6

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

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.
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http://dx.doi.org/10.1021/tx9003819DOI Listing
March 2010

DNA methylation by dimethyl sulfoxide and methionine sulfoxide triggered by hydroxyl radical and implications for epigenetic modifications.

Bioorg Med Chem Lett 2010 Jan 30;20(1):260-5. Epub 2009 Oct 30.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

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.
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http://dx.doi.org/10.1016/j.bmcl.2009.10.124DOI Listing
January 2010

Urea, the most abundant component in urine, cross-reacts with a commercial 8-OH-dG ELISA kit and contributes to overestimation of urinary 8-OH-dG.

Free Radic Biol Med 2009 Jul 3;47(1):41-6. Epub 2009 Mar 3.

Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.

Urinary 8-OH-dG is commonly analyzed as a marker of oxidative stress. For its analysis, ELISA and HPLC methods are generally used, although discrepancies in the data obtained by these methods have often been discussed. To clarify this problem, we fractionated human urine by reverse-phase HPLC and assayed each fraction by the ELISA method. In addition to the 8-OH-dG fraction, a positive reaction was observed in the first eluted fraction. The components in this fraction were examined by the ELISA. Urea was found to be the responsible component in this fraction. Urea is present in high concentrations in the urine of mice, rats, and humans, and its level is influenced by many factors. Therefore, certain improvements, such as a correction based on urea content or urease treatment, are required for the accurate analysis of urinary 8-OH-dG by the ELISA method. In addition, performance of the ELISA at 4 degrees C reduced the recognition of urea considerably and improved the 8-OH-dG analysis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2009.02.017DOI Listing
July 2009

[Difference in expression of VEGF, bFGF and their receptors between the young and postmenopausal women with breast cancer].

Zhonghua Zhong Liu Za Zhi 2003 Mar;25(2):141-4

Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Objective: To study the difference in the expression of VEGF, bFGF and their receptors between young and postmenopausal women with breast cancer.

Methods: The expression of VEGF, FLK-1, bFGF and FLG in 40 young and 30 postmenopausal women with breast cancer was studied by immunohistochemical method (SABC), with its relation with axillary lymph node metastasis and the clinical and pathologic characteristics. The expression index between these two groups was compared.

Results: The positive axillary lymph node rate and the mean expression of VEGF, bFGF in the young group were higher than postmenopausal group (P < 0.01 and P < 0.05), respectively. The mean expression of VEGF, bFGF, FLK-1 and FLG of axillary lymph node positive patients was higher than the negative ones both in young and postmenopausal women groups (P < 0.05 and P < 0.01). There was also a significant difference in VEGF, bFGF, FLK-1, FLG and MVC between the stage 0 - II and stage III - IV (P < 0.05 and P < 0.01) in both groups.

Conclusion: Breast cancer angiogenesis, characterized by the high expression of VEGF and bFGF, is directly correlated with the high tumor aggressiveness in the young women.
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March 2003
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