Publications by authors named "Hiroshi Kasai"

105 Publications

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

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

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

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

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

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

What causes human cancer? Approaches from the chemistry of DNA damage.

Authors:
Hiroshi Kasai

Genes Environ 2016 1;38:19. Epub 2016 Jul 1.

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

To prevent human cancers, environmental mutagens must be identified. A common mechanism of carcinogenesis is DNA damage, and thus it is quite possible that environmental mutagens can be trapped as adducts by DNA components. It is also important to identify new types of DNA damaging reactions and clarify their mechanisms. In this paper, I will provide typical examples of our efforts to identify DNA damage by environmental agents, from chemistry-based studies. 1) Oxidative DNA damage: 8-Hydroxydeoxyguanosine (8-OHdG, 8-oxodG) was discovered during a structural study of DNA modifications caused in vitro by heating glucose, which was used as a model of cooked foods. We found that various oxygen radical-forming agents induced the formation of 8-OHdG in DNA, in vitro and in vivo. Analyses of the urinary 8-OHdG levels are useful to assess the extent of oxidative DNA damage in a human population. 2) Lipid peroxide-derived DNA adducts: We searched for mutagens that react with deoxynucleosides, in model systems of lipid peroxidation. The reaction mixtures were analyzed by high performance liquid chromatography (HPLC), and we discovered various lipid peroxide-derived mutagens, including new mutagens. Some of these adducts were detected in human DNA. These mutagens may be involved in lipid peroxide-related cancers. 3) Methylation of cytosine by free radicals: Methylation of the cytosine C-5 position is an important mechanism of carcinogenesis, in addition to gene mutations. However, the actual mechanisms of de novo methylation in relation to environmental agents are not clear. We found that cytosine C-5 methylation occurred by a free radical mechanism. The possible role of this radical-induced DNA methylation in carcinogenesis will be discussed, in relation to the presently accepted concept of cancer epigenetics. In these studies, chemical analyses of the adducts formed in model reactions led to the discoveries of new mutagens and important types of DNA modifications, which seem to be involved in human carcinogenesis.
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http://dx.doi.org/10.1186/s41021-016-0046-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929788PMC
July 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 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

Lower serum levels of total cholesterol are associated with higher urinary levels of 8-hydroxydeoxyguanosine.

Nutr Metab (Lond) 2013 Oct 2;10(1):59. Epub 2013 Oct 2.

Department of Epidemiology and Prevention, Clinical Research Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.

Background: Lower serum total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterols (LDL-C) have been linked to an increased risk of cancer in various sites, but its underlying mechanism remains unclear. In an attempt to clarify the association between cholesterol levels and oxidative DNA damage, we investigated the relationship between serum cholesterol and urinary 8-hydroxydeoxyguanosine levels in a Japanese working population.

Methods: The study subjects were 294 men and 209 women aged 21-66 years in two Japanese municipal offices. Urinary 8-hydroxydeoxyguanosine (8-OHdG) was measured using an automated high-pressure liquid chromatography. Linear regression analysis was used to examine the associations of urinary 8-OHdG with TC, HDL-C and LDL-C levels with adjustment for sex, age, smoking and body mass index. Subgroup analyses were conducted by smoking status in men and age in women. Analysis of covariance was employed to estimate adjusted means of urinary 8-OHdG across TC category.

Results: After multivariate adjustment, urinary 8-OHdG levels were inversely associated with serum TC levels (β = -0.0015, p < 0.05) and LDL-C levels (β = -0.0012, p = 0.07). The inverse association with TC was apparent among smoking men (β = -0.0017, p < 0.05) and among women aged less than 48 years (β = -0.0040, p < 0.01). 8-OHdG decreased as TC increased (up to 219 mg/dL); subjects with TC levels of <160 mg/dL had a 17.4% higher adjusted mean of 8-OHdG than did those with TC levels of 200-219 mg/dL.

Conclusion: Results suggest that circulating low TC levels are associated with higher oxidative DNA damage.
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http://dx.doi.org/10.1186/1743-7075-10-59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850899PMC
October 2013

Identification of octenal-related dA and dC adducts formed by reactions with a hemin-ω-6-fat peroxidation model system.

Chem Res Toxicol 2013 Oct 1;26(10):1554-60. Epub 2013 Oct 1.

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

Deoxynucleosides were reacted in a lipid peroxidation model system, emulsified hemin-ethyl linoleate, and the adducts thus produced were analyzed by HPLC. Substantial amounts of stable adducts were detected in the dA- and dC-reaction mixtures. The structures of the major dA and dC adducts, other than the known 4-oxo-2-nonenal adducts, were determined to be etheno-type adducts, with a C₆ side chain bearing an α-hydroxyl-group. These results suggested that the substance involved in adduct formation is 2,3-epoxyoctanal. This compound showed mutagenicity in Salmonella strains TA 100 and TA 104 without the S-9 mix. In addition, based on the structure of a minor dC adduct, another possibly involved mutagen, 4-oxo-2-octenal, was proposed. These mutagens may be formed during storage and cooking of food, or during digestion, and may be involved in human cancers.
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http://dx.doi.org/10.1021/tx400245aDOI Listing
October 2013

Magnetic nanoparticles of Fe3O4 enhance docetaxel-induced prostate cancer cell death.

Int J Nanomedicine 2013 19;8:3151-60. Epub 2013 Aug 19.

Laboratory for Medical Engineering, Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama, Japan.

Docetaxel (DTX) is one of the most important anticancer drugs; however, the severity of its adverse effects detracts from its practical use in the clinic. Magnetic nanoparticles of Fe3O4 (MgNPs-Fe3O4) can enhance the delivery and efficacy of anticancer drugs. We investigated the effects of MgNPs-Fe3O4 or DTX alone, and in combination with prostate cancer cell growth in vitro, as well as with the mechanism underlying the cytotoxic effects. MgNPs-Fe3O4 caused dose-dependent increases in reactive oxygen species levels in DU145, PC-3, and LNCaP cells; 8-hydroxydeoxyguanosine levels were also elevated. MgNPs-Fe3O4 alone reduced the viability of LNCaP and PC-3 cells; however, MgNPs-Fe3O4 enhanced the cytotoxic effect of a low dose of DTX in all three cell lines. MgNPs-Fe3O4 also augmented the percentage of DU145 cells undergoing apoptosis following treatment with low dose DTX. Expression of nuclear transcription factor κB in DU145 was not affected by MgNPs-Fe3O4 or DTX alone; however, combined treatment suppressed nuclear transcription factor κB expression. These findings offer the possibility that MgNPs-Fe3O4-low dose DTX combination therapy may be effective in treating prostate cancer with limited adverse effects.
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http://dx.doi.org/10.2147/IJN.S40766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753150PMC
April 2014

Effects of Fe3O4 Magnetic Nanoparticles on A549 Cells.

Int J Mol Sci 2013 Jul 25;14(8):15546-60. Epub 2013 Jul 25.

Laboratory for Medical Engineering, Division of Materials and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama 240-8501, Japan.

Fe3O4 magnetic nanoparticles (MgNPs-Fe3O4) are widely used in medical applications, including magnetic resonance imaging, drug delivery, and in hyperthermia. However, the same properties that aid their utility in the clinic may potentially induce toxicity. Therefore, the purpose of this study was to investigate the cytotoxicity and genotoxicity of MgNPs-Fe3O4 in A549 human lung epithelial cells. MgNPs-Fe3O4 caused cell membrane damage, as assessed by the release of lactate dehydrogenase (LDH), only at a high concentration (100 μg/mL); a lower concentration (10 μg/mL) increased the production of reactive oxygen species, increased oxidative damage to DNA, and decreased the level of reduced glutathione. MgNPs-Fe3O4 caused a dose-dependent increase in the CD44+ fraction of A549 cells. MgNPs-Fe3O4 induced the expression of heme oxygenase-1 at a concentration of 1 μg/mL, and in a dose-dependent manner. Despite these effects, MgNPs-Fe3O4 had minimal effect on cell viability and elicited only a small increase in the number of cells undergoing apoptosis. Together, these data suggest that MgNPs-Fe3O4 exert little or no cytotoxicity until a high exposure level (100 μg/mL) is reached. This dissociation between elevated indices of cell damage and a small effect on cell viability warrants further study.
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http://dx.doi.org/10.3390/ijms140815546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759872PMC
July 2013

Serum vitamin B6, folate, and homocysteine concentrations and oxidative DNA damage in Japanese men and women.

Nutrition 2013 Oct 22;29(10):1219-23. Epub 2013 Jun 22.

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

Objective: Higher vitamin B status has been linked to a lower risk for cancer, but the underlying mechanism remains elusive. The aim of the present study was to examine the association of pyridoxal, folate, and homocysteine (Hcy) with urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage.

Methods: The participants were 500 employees (293 men and 207 women), ages 21 to 66 y, of two municipal offices in Japan. Serum pyridoxal and Hcy concentrations were measured using high-performance liquid chromatography (HPLC) method, and serum folate concentrations were measured using chemiluminescent immunoassay. Urinary 8-OHdG concentrations were measured using HPLC method. Multiple regression was used to estimate means of 8-OHdG for each tertile of pyridoxal, folate, and Hcy with adjustment for potential confounders.

Results: In multivariate analysis, 8-OHdG concentration was inversely associated with pyridoxal concentration in men (P for trend = 0.045) but not in women. The association in men was confined to non-smokers (P for trend = 0.033) or those who consumed no or < 20 g/d of ethanol (P for trend = 0.048). 8-OHdG concentrations were not appreciably associated with folate and Hcy concentrations.

Conclusion: The results suggest that vitamin B6, but not folate and homocysteine, plays a role against oxidative DNA damage in Japanese men.
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http://dx.doi.org/10.1016/j.nut.2013.03.014DOI Listing
October 2013

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

Distributions and ranges of values of blood and urinary biomarker of inflammation and oxidative stress in the workers engaged in office machine manufactures: evaluation of reference values.

Clin Chem Lab Med 2013 Feb;51(2):421-8

Department of Hematology and Oncology, Tokai University Hachioji Hospital, Tokai University School of Medicine, 192-0032, Tokyo, Japan.

Background: Interleukins, interferons and oxidative DNA products are important biomarkers assessing the inflammations and tissue damages caused by toxic materials in the body. We tried to evaluate distributions, reference values and age related changes of blood levels of inflammatory cytokines, C-reactive protein (CRP), IgE and urine levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) among workers in a cohort study evaluating the health influences of toner particles.

Methods: A total of 1366 male workers under age 50 years (age 19-49 years; 718 exposed and 648 not exposed to toner particles) in a cross sectional study of 1614 (categorized as 809 exposed and 805 not exposed, age 19-59 years) workers in a photocopier company has been followed prospectively as the cohort. Blood levels of interleukin (IL)-4, IL-6, IL-8, interferon-γ (IFN-γ), CRP, IgE and urine 8-OHdG were measured annually for 5 years.

Results: Reference values of the biomarkers are; CRP: 0.01-0.63×10(-2) g/L, IgE: 6-1480 IU/mL, IL-4: 2.6-76.1 pg/mL, IL-6: 0.4-4.9 pg/mL and 8-OHdG: 1.5-8.2 ng/mgCr. We could not evaluate reference values for IL-8 and IFN- γ because most of the values were below the sensitivity limits (2.0 pg/mL and 0.1 IU/mL, respectively). There were no differences of the biomarker levels between the toner exposed and the control workers. We observed a statistically significant age related decrease of serum IL-4 levels.

Conclusions: This is the first report assessing the distributions and reference values of inflammatory biomarker levels in a large scaled cohort. We observed age related changes of some of the biomarkers. We could not detect any differences of the studied biomarker values between the toner exposed and the control workers.
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http://dx.doi.org/10.1515/cclm-2012-0330DOI Listing
February 2013

Depressive symptoms and oxidative DNA damage in Japanese municipal employees.

Psychiatry Res 2012 Dec 23;200(2-3):318-22. Epub 2012 Jun 23.

Department of Epidemiology and International Health, International Clinical Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

We sought to explore the relationship between depressive symptoms and urinary 8-hydroxydeoxyguanine (8-OHdG), a biomarker of systemic oxidative DNA damage and repair, among 301 men and 210 women aged 21-67 years working in two municipal offices. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale (CES-D). The geometric mean and its 95% confidence interval (CI) of urinary 8-OHdG concentrations were calculated according to the quartile of CES-D score. The prevalence of depressive symptoms, defined as having CES_D of ≥16, was 35.9% in men and 35.2% in women. There was no significant difference in geometric mean of urinary 8-OHdG concentrations according to the levels of depressive symptoms. In men, the multivariable-adjusted geometric mean of urinary 8-OHdG concentrations (95% CIs) in the first, second, third, and fourth category of depressive symptoms was 1.09 (1.02-1.16), 1.16 (1.08-1.24), 1.15 (1.07-1.24), and 1.10 (1.02-1.18), respectively (p for trend=0.86). Similarly, no significant association was found in the analyses among women, nonsmoking men, and smoking men. The lack of association between depressive symptoms and urinary 8-OHdG concentrations may indicate the absence or more complex interactions between milder forms of depression and systemic oxidative DNA damage and repair in well-functioning population.
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http://dx.doi.org/10.1016/j.psychres.2012.05.035DOI Listing
December 2012

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

PUFAs in serum cholesterol ester and oxidative DNA damage in Japanese men and women.

Am J Clin Nutr 2012 May 21;95(5):1209-14. Epub 2012 Mar 21.

Department of Nutrition and Life Science, Faculty of Life Science and Biotechnology, Fukuyama University, Fukuyama, Japan.

Background: PUFAs are susceptible to lipid peroxidation and play a role in inflammation, both of which can induce oxidative stress. However, the relation of PUFA to oxidative DNA damage in humans is elusive.

Objective: We examined the association between concentrations of circulatory PUFAs and urinary 8-oxo-7,8-dihydroguanine (8-oxoGua) in Japanese men and women.

Design: The subjects were 495 participants (290 men and 205 women) in a cross-sectional study in 2 municipal offices in Japan. Serum cholesterol ester (CE) and phospholipid fatty acid composition were measured by gas-liquid chromatography. Urinary 8-oxoGua concentrations were measured by HPLC, and 8-oxoGua values for each tertile of PUFA after adjustment for covariates were calculated by multiple regression.

Results: Urinary 8-oxoGua concentrations increased with increasing concentrations of n-3 (omega-3) PUFAs, EPA, and DHA in serum CE (P-trend = 0.001, 0.01, and 0.009, respectively), whereas they decreased with increasing concentrations of n-6 PUFAs and linoleic acid (P-trend = 0.02 and 0.051, respectively).

Conclusion: Oxidative DNA damage may be greater with higher concentrations of long-chain n-3 PUFAs but lower with higher concentrations of n-6 (omega-6) PUFAs.
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http://dx.doi.org/10.3945/ajcn.111.030817DOI Listing
May 2012

Association between 8-oxo-7,8-dihydroguanine excretion and risk of lung cancer in a prospective study.

Free Radic Biol Med 2012 Jan 20;52(1):167-72. Epub 2011 Oct 20.

Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.

Oxidative damage to guanine (8-oxoGua) is one of the most abundant lesions induced by oxidative stress and documented mutagenic. 8-Oxoguanine DNA glycosylase 1 (OGG1) removes 8-oxoGua from DNA by excision. The urinary excretion of 8-oxoGua is a biomarker of exposure, reflecting the rate of damage in the steady state. The aim of this study was to investigate urinary 8-oxoGua as a risk factor for lung cancer. In a nested case-cohort design we examined associations between urinary excretion of 8-oxoGua and risk of lung cancer as well as potential interaction with the OGG1 Ser326Cys polymorphism in a population-based cohort of 25,717 men and 27,972 women aged 50-64 years with 3-7 years follow-up. We included 260 cases with lung cancer and a subcohort of 263 individuals matched on sex, age, and smoking duration for comparison. Urine collected at entry was analysed for 8-oxoGua by HPLC with electrochemical detection. There was no significant effect of smoking or OGG1 genotype on the excretion of 8-oxoGua. Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer was 1.06 (0.97-1.15) per doubling of 8-oxoGua excretion. The association between lung cancer risk and 8-oxoGua excretion was significant among men [IRR: 1.17 (1.03-1.31)], never-smokers [IRR: 9.94 (1.04-94.7)], and former smokers [IRR: 1.19 (1.07-1.33)]. There was no significant interaction with the OGG1 genotype, although the IRR was 1.14 (0.98-1.34) among subjects homozygous for Cys326. The association between urinary 8-oxoGua excretion and lung cancer risk among former and never-smokers suggests that oxidative stress with damage to DNA is important in this group.
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http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.439DOI Listing
January 2012

Inhibition by wheat sprout (Triticum aestivum) juice of bisphenol A-induced oxidative stress in young women.

Mutat Res 2011 Sep 28;724(1-2):64-8. Epub 2011 Jun 28.

Sookmyung Women's University, College of Pharmacy, Seoul 140-742, Republic of Korea.

For health of future generation, fertile young women should be monitored for exposure of endocrine disrupting chemicals (EDCs). Among EDCs, bisphenol A (BPA) is suggested to induce reactive oxygen species (ROS) which play an important role in pathologies of female diseases such as endometriosis. On the other hand, previous studies suggested that sprouts of wheat (Triticum aestivum) have antimutagenicity and antioxidant activity. We performed the 2 weeks intervention of wheat sprout juice (100ml/day) to investigate its effects on BPA-exposure and -oxidative toxicity in young women (N=14, age=24.4±4.0). Geometrical mean of urinary BPA levels was 1.81 (GSTD, 4.34)μg/g creatinine. We observed that irregular meals significantly increased levels of urinary BPA approximate 3 times (p=0.03). In addition, we found BPA-induced oxidative stress is correlated with levels of 8-hydroxydeoxyguanosine (8-OHdG) or malondialdehyde (MDA) levels (p=0.18 or 0.03, respectively). We also observed a continuous reduction of urinary BPA during the wheat sprout intervention (p=0.02). In summary, our data suggested potential detoxification of wheat sprouts on BPA-toxicity via antioxidative and interference of absorption, distribution, metabolism and excretion (ADME)-mediated mechanisms in young women.
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http://dx.doi.org/10.1016/j.mrgentox.2011.06.007DOI Listing
September 2011

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

8-Hydroxyguanine levels and repair capacity during mouse embryonic stem cell differentiation.

Free Radic Res 2011 May 4;45(5):527-33. Epub 2011 Feb 4.

Department of Chemical Processes and Environments, Faculty of Environmental Engineering, The University of Kitakyushu, Kitakyushu, Fukuoka, 808-0135, Japan.

To evaluate the defence capacities of embryonic stem (ES) cells against gene impairment, this study measured the levels of 8-hydroxyguanine (8-OH-Gua), a well-known marker of oxidative stress in DNA, and its repair capacity during differentiation. Undifferentiated ES cells (EB3) were cultured without leukaemia inhibitory factor (LIF) for 0, 4 and 7 days and are referred to as ES-D0, ES-D4 and ES-D7, respectively. These three cell lines were treated with 300 μM hydrogen peroxide (H(2)O(2)) for 48 and 72 h. After treatment, the amounts of 8-OH-Gua in the cells were determined by the high-performance liquid chromatography (HPLC)-electrochemical detector (ECD) method. The levels of 8-OH-Gua in ES-D7 treated with H(2)O(2) were higher than those in ES-D0 and ES-D4, suggesting that the DNA in the undifferentiated cells was protected against gene impairment, as compared to that in the differentiated cells. To examine the repair capacity for 8-OH-Gua, this study analysed the expression of 8-OH-Gua repair-associated genes, 8-oxoguanine DNA glycosylase 1 (OGG1), MutY homolog (MUTYH) and Mut T homolog 1 (MTH1), in ES-D0, ES-D4 and ES-D7. The mRNA levels of MUTYH and MTH1 showed no significant change, whereas OGG1 mRNA was significantly decreased in ES-D7 treated with H(2)O(2). Moreover, it was observed that ES-D7 treated with H(2)O(2) readily underwent apoptosis, in comparison to its undifferentiated counterparts, ES-D0 and ES-D4. Taken together, ES cells are more resistant to DNA oxidative stresses than differentiated cells.
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http://dx.doi.org/10.3109/10715762.2011.555481DOI Listing
May 2011
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