Publications by authors named "Kazuaki Kawai"

76 Publications

Detection and structural analysis of pyrimidine-derived radicals generated on DNA using a profluorescent nitroxide probe.

Chem Commun (Camb) 2021 Dec 21;58(1):56-59. Epub 2021 Dec 21.

Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.

The oxidative damage of DNA is associated with aging and the development of various diseases. Although nucleoside-derived radicals play an important role in DNA oxidation, their analysis methods are limited. Herein, we propose a fluorometric detection and structural analysis of radicals on the surface of oxidatively damaged DNA using a profluorescent nitroxide probe combined with liquid chromatography-fluorometry and high-resolution tandem mass spectrometry.
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http://dx.doi.org/10.1039/d1cc04998dDOI Listing
December 2021

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

Free radical-mediated acetaldehyde formation by model reactions of dietary components: effects of meat, wine, cooking oil and coffee.

Genes Environ 2021 Jul 9;43(1):28. Epub 2021 Jul 9.

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

Background: Alcohol consumption and the ingestion of red meat and oxidized cooking oil are risk factors of gastric and colorectal cancers. We reported that acetaldehyde (AcAld) is generated from Heme/Mb/Meat-Linoleate-EtOH model reaction mixtures, and thus could be a new plausible mechanism for the carcinogenesis (Kasai and Kawai, ACS Omega, 2021).

Results: In this study, we investigated the effects of wine and coffee, in addition to meat components, on this reaction. Depending on the conditions, such as pH, reaction time and choice of free hemin, myoglobin (Mb), as well as meat extracts (raw meat, baked meat, salami), wine and coffee enhanced AcAld formation. Polyphenols in red wine and coffee may stimulate AcAld formation by acting as pro-oxidants in the presence of Heme/Mb/Meat. In a model reaction of Mb + EtOH + HO, we observed time-dependent AcAld formation. In support of these in vitro data, after the consumption of a red meat-rich diet with red wine, the fecal AcAld level significantly increased as compared to the levels associated with a diet of fish + wine, or red meat without alcohol.

Conclusions: These results suggested that AcAld generation from dietary components may be an important mechanism of gastrointestinal tract carcinogenesis.
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http://dx.doi.org/10.1186/s41021-021-00201-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268395PMC
July 2021

New Plausible Mechanism for Gastric and Colorectal Carcinogenesis: Free Radical-Mediated Acetaldehyde Generation in a Heme/Myoglobin-Linoleate-Ethanol Mixture.

ACS Omega 2021 May 28;6(18):12014-12021. Epub 2021 Apr 28.

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu 8078555, Japan.

Epidemiological studies have revealed that alcohol, red meat, and cooking oil (or linoleate) are risk factors for both gastric and colon cancers. A survey of the mutation spectra of the p53 tumor suppressor gene in these cancers suggested that the types of mutations and the hot spots are similar to those induced by acetaldehyde (AcAld) in an in vitro p53 mutation analysis system. Accordingly, various combinations of possible factors, components, or model compounds were reacted in an emulsion and tested for the generation of AcAld. Efficient AcAld formation was only observed with combinations of three factors, red meat homogenate (or heme/myoglobin), methyl linoleate, and ethanol, but not by any combination of the two. The generated AcAld levels (ca. 500 μM) far exceeded the minimum mutagenic concentration (40-100 μM) obtained using concentrations of meat homogenate (or heme/Mb), linoleate, and ethanol comparable to those in the stomach after an ordinary meal. A mutagenic level of AcAld (75 μM) was also generated with a physiological concentration of ethanol, heme, and linoleate in the colon. As a mechanism, linoleate hydroperoxide formation and its decomposition in the presence of myoglobin (or heme) to generate the OH radical seem to be involved in the ethanol-to-AcAld conversion.
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http://dx.doi.org/10.1021/acsomega.1c00614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153976PMC
May 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

Salivary 8-hydroxyguanine as a lifestyle-related oxidative stress biomarker in workers.

J Clin Biochem Nutr 2020 Jan 1;66(1):57-61. Epub 2020 Jan 1.

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

Oxidative stress is a risk factor for lifestyle-related diseases, such as cancer. Investigations of the factors that increase or decrease oxidative stress contribute to disease prevention. In the present study, we focused on the 8-hydroxyguanine (8-OHGua) in saliva, as a new oxidative stress biomarker. The relationship between lifestyles and salivary 8-OHGua levels in 541 Japanese subjects was analyzed. The salivary 8-OHGua levels were significantly elevated in older persons, as well as those who smoke, have hypertension, or excess visceral fat. By contrast, statistically significant lower levels of 8-OHGua were observed in persons who moderately exercised or recently drank green tea or coffee. The direct collection of saliva, without any special collecting device, was suitable for the 8-OHGua analysis. The present results suggest that oxidative stress can be measured in a non-invasive manner with easily collectable saliva, and the salivary 8-OHGua may be a useful biomarker for lifestyle-related disease prevention.
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http://dx.doi.org/10.3164/jcbn.19-72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983431PMC
January 2020

Diurnal variation of salivary oxidative stress marker 8-hydroxyguanine.

Genes Environ 2019 10;41:20. Epub 2019 Dec 10.

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

Introduction: Oxidative stress is a risk factor for life-style related diseases, including cancer. We recently reported that the oxidative stress marker 8-hydroxyguanine (8-OHGua) can be measured in saliva non-invasively. Understanding the diurnal pattern of salivary 8-OHGua levels is crucial for evaluating the oxidative stress. In this study, we analyzed the diurnal variation of salivary 8-OHGua levels.

Findings: The salivary 8-OHGua levels were relatively stable in the daytime (10:00-22:00). The daytime 8-OHGua levels seemed to represent the individual oxidative stress status. The average amount and the variation of the salivary 8-OHGua levels immediately after awakening were higher than those of the daytime levels.

Conclusions: The 8-OHGua levels in saliva exhibited diurnal variation. The levels were higher at the time of awakening. At this point, the daytime levels of salivary 8-OHGua may be appropriate for evaluating the individual oxidative stress status. Further study is needed for understanding and utilizing the 8-OHGua levels at the time of awakening.
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http://dx.doi.org/10.1186/s41021-019-0138-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902586PMC
December 2019

[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

Pyrimidine Ring-Opened Product from Oxidative DNA Damage of 5-Formyl-2'-deoxyuridine.

Chem Res Toxicol 2019 04 27;32(4):737-744. Epub 2019 Feb 27.

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

After thymidine (dT) was treated with a Fenton-type reagent and further incubated for a long period (6 days) under physiological conditions (37 °C, pH 7.4), a new product, named dT*, was detected by HPLC in addition to the free thymine base and the known oxidative dT damage, 5-formyl-2'-deoxyuridine (fdU). dT* was found to be formed from fdU. The structure of dT* was determined to be 3-amino-2-carbamoyl-2-propenal-N-2'-deoxyriboside, a pyrimidine ring-opened product from fdU, on the basis of H- and C NMR analyses and mass spectra. From the model compound 1-methyl-5-formyluracil, a similar ring-opened product was formed after the incubation. dT* was also detected in DNA treated with a Fenton-type reagent or γ-rays, followed by the prolonged incubation. dT* will be a new promising marker of oxidative DNA damage. The possible role of this product in oxy-radical-induced mutagenesis is discussed.
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http://dx.doi.org/10.1021/acs.chemrestox.8b00401DOI Listing
April 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

Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas.

Int J Mol Sci 2017 Feb 17;18(2). Epub 2017 Feb 17.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan.

To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV⁺ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1), and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.
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http://dx.doi.org/10.3390/ijms18020434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343968PMC
February 2017

Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives.

Biomed Res Int 2017 16;2017:4245309. Epub 2017 Jan 16.

University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu 807-8555, Japan.

We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 m) at three mass concentrations of 1, 4, and 16 mg/m for 22.5 months, and the rats were sacrificed after 6 months, 12 months, and 22.5 months of exposure. The low and medium concentrations did not induce statistically significant pulmonary inflammation, but the high concentration did, and, in addition, a histopathological examination showed fibrosis in the lung. Although lung tumor was observed in one sample of high exposure for 22.5 months, the cause was not statistically significant. On the other hand, a persistent increase in 8-OHdG was observed in the high exposure group, indicating that DNA damage by oxidative stress with persistent inflammation leads to the formation of tumorigenesis. The results of our studies show that toners with external additives lead to pulmonary inflammation, oxidative stress, and fibrosis only at lung burdens beyond overload. These data suggest that toners with external additives may have low toxicity in the lung.
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http://dx.doi.org/10.1155/2017/4245309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278518PMC
February 2017

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

Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation.

Int J Mol Sci 2016 Aug 1;17(8). Epub 2016 Aug 1.

National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan.

We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m³) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.
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http://dx.doi.org/10.3390/ijms17081241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000639PMC
August 2016

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation.

J Nanopart Res 2015;17(11):442. Epub 2015 Nov 13.

National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565 Japan.

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO nanoparticles (2, 10 mg/m, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.
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http://dx.doi.org/10.1007/s11051-015-3249-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644191PMC
November 2015

Comparison of pulmonary inflammatory responses following intratracheal instillation and inhalation of nanoparticles.

Nanotoxicology 2016 11;10(5):607-18. Epub 2015 Nov 11.

c National Institute of Advanced Industrial Science and Technology , Tsukuba , Japan .

In order to examine whether intratracheal instillation studies can be useful for determining the harmful effect of nanoparticles, we performed inhalation and intratracheal instillation studies using samples of the same nanoparticles. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In the intratracheal instillation study, rats were exposed to 0.2 or 1 mg of NiO or TiO2. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the single intratracheal instillation. In the inhalation study, rats were exposed to inhaled NiO or TiO2 (1.65, 1.84 mg/m(3), respectively) for 4 weeks. The same endpoints were examined from 3 days to 3 months after the end of exposure. Inhalation of NiO induced an increase in the number of neutrophils in BALF and concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and heme oxygenase (HO)-1. Intratracheal instillation of NiO induced persistent inflammation and upregulation of these cytokines was observed in the rats. However, inhalation of TiO2 did not induce pulmonary inflammation, and intratracheal instillation of TiO2 transiently induced an increase in the number of neutrophils in BALF and the concentrations of CINC-1, CINC-2 and HO-1. Taken together, a difference in pulmonary inflammation was observed between the high and low toxicity nanomaterials in the intratracheal instillation studies, as in the inhalation studies, suggesting that intratracheal instillation studies may be useful for ranking the harmful effects of nanoparticles.
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http://dx.doi.org/10.3109/17435390.2015.1104740DOI Listing
November 2016

Coffee intake is associated with lower levels of oxidative DNA damage and decreasing body iron storage in healthy women.

Nutr Cancer 2014 25;66(6):964-9. Epub 2014 Jul 25.

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

Habitual coffee drinking has been linked to a lower risk for some forms of cancer, but the mechanism remains elusive. Coffee may decrease oxidative DNA damage, an important pathway to carcinogenesis. We examined the association between coffee consumption and urinary 8-hydroxydeoxyguanosine (8-OHdG) concentrations, a biomarker of systemic oxidative DNA damage and repair, in 507 healthy subjects (298 men and 209 women aged 21-67 yr) while adjusting for age, sex, smoking status, body mass index, job type, and fasting blood glucose in multivariable regression models. The association with green tea consumption was also assessed. Urinary 8-OHdG concentrations tended to decrease with coffee consumption in women (trend P = 0.046), with women drinking 2-3 cups of coffee per day showing the lowest mean of urinary 8-OHdG concentrations. This association was largely attenuated after further adjustment for serum ferritin concentrations, a marker of body iron storage (trend P = 0.96). Green tea consumption was not associated with urinary 8-OHdG concentrations. Coffee drinking may be associated with decreased systemic oxidative DNA damage through decreasing body iron storage in women.
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http://dx.doi.org/10.1080/01635581.2014.932398DOI Listing
April 2015

Somatic cell mutations caused by 365 nm LED-UVA due to DNA double-strand breaks through oxidative damage.

Photochem Photobiol Sci 2014 Sep;13(9):1338-46

Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsushima, Okayama, Japan.

Evidence is accumulating indicating that UVA (320-400 nm ultraviolet light) plays an important role in photo-carcinogenesis. UVA is thought to produce reactive oxygen species in irradiated cells through photo-activation of inherent photosensitizers, and was recently reported to cause DNA double-strand breaks (DSBs) in exposed cells. We have investigated the involvement of UVA in mutations and DNA damage in somatic cells using Drosophila melanogaster larvae. Using the Okazaki Large Spectrograph, we previously observed that longer wavelength UVA (>330 nm) was more mutagenic in post-replication repair-deficient D. melanogaster (mei-41) than in the nucleotide excision repair-deficient strain (mei-9). LED-light has recently been developed as a high-dose-rate UVA source. LED-UVA light (365 nm) was also more mutagenic in mei-41 than in mei-9. The mei-41 gene was shown to be an orthologue of the human ATR gene, which is involved in the repair of DSBs through phosphorylation of histone H2AX. In order to estimate the extent to which oxidative damage contributes to mutation, we established a new D. melanogaster strain (urate-null mutant) that is sensitive to oxidative damage and has a marker to detect somatic cell mutations. When somatic cell mutations were examined using this strain, LED-UVA was mutagenic in the urate-null strain at doses that were non-mutagenic in the urate-positive strain. In an effort to investigate the generation of DSBs, we examined the presence of phosphorylated histone H2AvD (H2AX D. melanogaster homologue). At high doses of LED-UVA (>800 kJ m(-2)), levels of phosphorylated H2AvD (γ-H2AvD) increased significantly in the urate-null strain. Moreover, the level of γ-H2AvD increased in the excision repair-deficient strain but not in the ATR-deficient strain following UVA-irradiation. These results supported the notion that the generation of γ-H2AvD was mediated by the function of the mei-41 gene. It was reported that ATR functions on DSB repair in D. melanogaster. Taken together, we propose a possible pathway for UVA-induced mutation, whereby DNA double-strand breaks resulting from oxidative stress might be responsible for UVA-induced mutation in somatic cells of D. melanogaster larvae.
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http://dx.doi.org/10.1039/c4pp00148fDOI Listing
September 2014

Urinary 1-hydroxypyrene levels among office workers living in industrial areas.

J UOEH 2014 Mar;36(1):1-10

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

We examined exposure to polycyclic aromatic hydrocarbons (PAHs) among non-smoking office workers in 2 countries living in the vicinity of a coke-oven factory by measuring their levels of urinary 1-OHP, a known metabolite of PAHs. Subjects included 10 non-smoking office workers in Kitakyushu city (Japan) and 20 workers in Thai Nguyen city (Vietnam). Measurement was optimized by using the high-performance liquid chromatography (HPLC) method developed by Jongeneelen et al. This method required only a small amount of urine and had a short incubation time, and its detection limit was very low (0.00448 ng/ml), which was practical and highly sensitive.The median urinary 1-OHP concentration in the Vietnamese subjects (0.417 ng/mg creatinine) was six times as high as that in the Japanese subjects (0.069 ng/mg creatinine) (P < 0.001). However, both concentrations were significantly below the guideline level, below which there is no genotoxic effect, implying a low probability of any adverse health effects.Our measurements from both countries showed higher urinary 1-OHP concentrations than in previous studies from locations without factories, indicating that ambient air pollution from industrial emissions is an important source of PAH exposure. Finally, the urinary 1-OHP concentrations did not correlate with gender or lifestyle factors.
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http://dx.doi.org/10.7888/juoeh.36.1DOI Listing
March 2014

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
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