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Featured researches published by Katsumaro Tomokuni.


Occupational and Environmental Medicine | 1970

Urinary excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene as a test of exposure

Masana Ogata; Katsumaro Tomokuni; Yohiko Takatsuka

Ogata, M., Tomokuni, K., and Takatsuka, Y. (1970).Brit. J. industr. Med.,27, 43-50. Urinary excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene as a test of exposure. Twenty-three male volunteers were exposed in groups of four or five to toluene and m- and p-xylene vapour for periods of 3 hours or of 7 hours with one break of an hour. Urine was collected at hourly intervals for several hours, and thereafter all urine was collected until 18 hours after the end of the exposure period, and was analysed for hippuric and methylhippuric acids. It was shown that hippuric acid was excreted equivalent to 68% of the toluene absorbed, and m-methylhippuric acid equivalent to 72% of the m-xylene absorbed. Up to hydrocarbon concentrations of 200 ppm the total quantity of hippuric acids excerted was proportional to the total exposure (ppm × hours). In descending order of precision the following were also related to exposure: rate of excretion during the exposure period; concentrations of hippuric acid in urine corrected to constant urine density; and concentrations in urine uncorrected for density. The last could not be used to calculate exposure, but the others could be to give screening tests to show whether workmen could have been exposed to concentrations greater than the maximum allowable. The effects of exposure on blood pressure, pulse rate, flicker value, and reaction time were measured. There were some variations which suggested that the MAC of toluene should be set higher than 200 ppm.


Occupational and Environmental Medicine | 1969

Quantitative determination in urine of hippuric acid and m- or p-methylhippuric acid, metabolites of toluene and m- or p-xylene

Masana Ogata; Katsumaro Tomokuni; Yoshiko Takatsuka

Ogata, M., Tomokuni, K., and Takatsuka, Y. (1969).Brit. J. industr. Med.,26, 330-334. Quantitative determination in urine of hippuric acid and m- or p-methylhippuric acid, metabolites of toluene and m- or p-xylene. Improved and more specific methods for the quantitative determination of hippuric and m- and p-methylhippuric acids in urine are described. The acids were extracted from urine with ether/ethanol, which was dried with silica gel, or with ethyl acetate. After removing the solvent by evaporation coloured azlactones were formed by reaction with p-dimethylaminobenzaldehyde in acetic anhydride (DAB, only usable after ether/ethanol extraction) or benzenesulphonyl chloride in pyridine, and the absorbances were measured. The sensitivities were about 4 μg./ml. of urine using DAB, and 20 μg./ml. of urine using benzenesulphonyl chloride reagent. Separation of hippuric and methylhippuric acids was achieved by paper and thin-layer chromatography before estimation. A spot test is also described.


Occupational and Environmental Medicine | 2001

Urinary 1-hydroxypyrene in coke oven workers relative to exposure, alcohol consumption, and metabolic enzymes

Jiusong Zhang; Masayoshi Ichiba; Kunio Hara; S Zhang; Tomoyuki Hanaoka; Guowei Pan; Yuko Yamano; Ken Takahashi; Katsumaro Tomokuni

OBJECTIVES To investigate the influence of personal lifestyle—such as smoking and alcohol consumption—on urinary 1-hydroxypyrene (1-OHP) concentrations in coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) and to evaluate the association of 1-OHP concentrations with the genetic polymorphism of several metabolic enzymes including cytochrome P-450 (CYP) 1A1 and glutathione S-tranferases (GSTs). METHODS The study population contained 162 coke oven workers and 58 controls employed at the largest iron and steel factory in China. Personal data were collected at the interview. 1-OHP in urine was measured with high performance liquid chromatography with fluorescence detection. Genetic polymorphisms were identified by the polymerase chain reaction (PCR) method. RESULTS A positive association between excretion of urinary 1-OHP and the levels of exposure to PAHs was confirmed. Those people who consumed ⩾50 g/day ethanol had significantly higher 1-OHP excretion than did other coke oven workers (p<0.01). No significant difference in urinary 1-OHP was found between smokers and non-smokers, in both controls and exposed subjects. The variant homozygotes at exon 7 of the CYP1A1 gene had significantly higher urinary 1-OHP concentrations than other CYP1A1 genotypes among the exposed workers (p=0.03). There was less association between the concentrations of 1-OHP and the GSTM1, GSTP1, or GSTT1 polymorphism. CONCLUSIONS The present study confirmed that urinary 1-OHP is a good biomarker for exposure to PAHs. Alcohol consumption affected urinary 1-OHP excretion. The variant genotypes of the CYP1A1 gene may result in the enhancement of PAH metabolites. It is helpful to understand the role of individual susceptibility on metabolism of carcinogens. These findings suggest that the modulating effect of individual lifestyle factors or genetic nature should be considered in future studies on occupational exposure to PAHs and in evaluating the health risk from harmful chemicals.


Mutation Research-genetic Toxicology and Environmental Mutagenesis | 2002

Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers.

Jeongmi Lee; Daehee Kang; Kyoung Ho Lee; Masayoshi Ichiba; Jiusong Zhang; Katsumaro Tomokuni; Eung-Soo Hwang; Chung Gyu Park; Mina Ha; SungGyun Kim; Sang Beom Han; Jae Wook Choi; Eunil Lee; Jae Yeon Jang; Paul T. Strickland; Ari Hirvonen; Soo Hun Cho

Waste incinerating workers are exposed to various pyrolysis products including polycyclic aromatic hydrocarbons (PAHs). We examined their PAH exposure by assessing urinary 1-hydroxypyrene glucuronide (1-OHPG), as a measure of internal dose, and aromatic DNA adducts in peripheral white blood cells (WBCs), as a measure of biological effect dose. The potential effect of genetic polymorphisms of three enzymes involved in PAH metabolisms (i.e., CYP1A1, GSTM1, and GSTT1) on these exposure markers was also investigated.Twenty-nine employees including workers incinerating industrial wastes and 21 non-exposed on-site controls were recruited from a company handling industrial wastes in South Korea. Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects working near incinerators. Urinary 1-OHPG was assayed by synchronous fluorescence spectroscopy (SFS) after immunoaffinity purification using monoclonal antibody 8E11. Aromatic DNA adducts in peripheral WBC were measured by the nuclease P1-enhanced post-labelling assay. Genotypes were assessed by PCR-based methods. Information on smoking habits and use of personal protective equipment were collected by self-administered questionnaire. Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (P=0.006, by Kruskal-Wallis test). A statistically significant dose-response increase in 1-OHPG levels was seen with the number of cigarettes consumed per day (r=0.686, P<0.001). Smoking and GSTM1 genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R(2)=0.565, P<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R(2)=0.249, P=0.201). Aromatic DNA adducts were significantly correlated with log-transformed urinary 1-OHPG level (r=0.31, P=0.04). However, the partial correlation coefficient adjusting for age, sex, and cigarette consumption was not significant (r=0.15, P=0.17). The significant association exists only in individuals with the GSTM1 null genotype (Pearsons correlation coefficient, r=0.52, P=0.01; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.36, P=0.04). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTM1 genotype. These results remain to be confirmed in future larger studies.


Mutation Research-genetic Toxicology and Environmental Mutagenesis | 2003

Multiple biomarkers study in painters in a shipyard in Korea.

Kyoung Ho Lee; Masayoshi Ichiba; Jiusong Zhang; Katsumaro Tomokuni; Yun-Chul Hong; Mina Ha; Ho Jang Kwon; Sang Back Koh; Hong Ryul Choi; Kwan-Hee Lee; Chung Gyu Park; Soo Hun Cho; Ari Hirvonen; Paul T. Strickland; Roel Vermeulen; Richard B. Hayes; Daehee Kang

Shipbuilding workers are exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs). A limited number of studies have been conducted to evaluate biomarkers related to PAH exposure in painters in the shipyard industry. We examined this in 208 workers recruited from a shipyard located in South Korea. Employees were grouped into three exposure groups: (1) 111 painters using coal tar paints, (2) 70 painters using general paints, and (3) 27 on-site controls using no paints. Levels of urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy. Glutathione S-transferase (GST) M1 and T1 genotypes were assessed by a multiplex polymerase chain reaction (PCR)-based method, aromatic-DNA adducts in peripheral white blood cells were measured by 32P-postlabeling, and glycophorin A (GPA) variant frequencies in red blood cells were assessed by flow cytometry. Information on demographic characteristics, smoking habits, diet, job title and use of personal protective equipment (e.g. respiratory and dermal) were collected by self-administered questionnaire. Average urinary 1-OHPG levels in coal tar paint (2.24 micromol/mol creatinine) and general paint (1.38 micromol/mol creatinine) users were significantly higher than in on-site controls (0.62 micromol/mol creatinine) (P<0.001). Paint use, irrespective of the type of paints, and smoking (yes/no) were positively associated with urinary 1-OHPG levels, whereas green tea consumption (yes/no) was negatively associated with the 1-OHPG levels. No significant effect in the 1-OHPG levels were observed for the GSTM1 and GSTT1 genotypes. Aromatic-DNA adduct levels tended to be higher in coal tar paint users (P = 0.06) and painters (P = 0.07) compared to on-site controls. No differences in adduct levels were observed, between the two groups of painters, and the combined group showed greater adduct levels than on-site controls (P = 0.05). GPA mutation frequencies measured in 55 individuals with MN heterozygote genotypes were not significantly different among the three exposure groups, and no correlation was observed between urinary 1-OHPG levels and aromatic-DNA adducts or GPA mutation frequency. These results suggest that painters in the shipyard were exposed to significant amounts of PAHs and possibly to other genotoxic aromatic compounds, and that urinary 1-OHPG may be a potential biomarker of PAH exposure in this population.


Occupational and Environmental Medicine | 1971

Excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene in an exposure chamber and in workshops, with specific reference to repeated exposures

Masana Ogata; Yoshiko Takatsuka; Katsumaro Tomokuni

Ogata, M., Takatsuka, Y., and Tomokuni, K. (1971).Brit. J. industr. Med.,28, 382-385. Excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene in an exposure chamber and in workshops, with specific reference to repeated exposures. Four male volunteers were exposed to 200 p.p.m. of toluene for five one-hour periods separated by one-hour intervals. The excretion curve of hippuric acid showed multi-peaks, and almost concided with a theoretical curve previously described. The fraction of the toluene absorbed which was accounted for as hippuric acid was only slightly lower than after a single exposure. In a paint spraying shop exposure was measured both from the concentrations of toluene in the air by a Kitagawa detector and from the exceretion of urinary hippuric acid. The results were in general agreement, with a correlation coefficient of 0·67. Urinary hippuric acid and methylhippuric acid were determined on urines from two workers in a shipbuilding yard who used paint thinned with toluene and xylene. The concentrations of the acids varied from day to day depending on the kind and the duration of work. From the concentrations found the mean concentrations to which the workers were exposed were calculated as a fraction of the maximum allowable concentration (M.A.C.). One worker was, on this evidence, exposed to more than the combined M.A.C. on three days out of six.


Occupational and Environmental Medicine | 1970

A simple method for the quantitative analysis of urinary trichloroethanol and trichloroacetic acid as an index of trichloroethylene exposure.

Masana Ogata; Yoshiko Takatsuka; Katsumaro Tomokuni

Ogata, M., Takatsuka, Y., and Tomokuni, K. (1970).Brit. J. industr. Med.,27, 378-381. A simple method for the quantitative analysis of urinary trichloroethanol and trichloroacetic acid as an index of trichloroethylene exposure. A simple method of estimating trichloroethanol and trichloroacetic acid in the urine of workers exposed to trichloroethylene is described. The glucuronide of trichloroethanol was hydrolysed enzymatically to trichloroethanol by β-glucuronidase and the trichloroethanol released was allowed to react with pyridine and potassium hydroxide in that order, thereby avoiding decomposition of trichloroethanol with strong alkali. The colour which developed in 3·5 minutes at 100°C with pyridine was measured at 440 nm and 530 nm. This also allowed trichloroacetic acid to be determined. The results agreed well with those obtained by longer methods.


Biomarkers | 2000

Inter-individual variation of smoking-related DNA adducts in lymphocytes-relationship to mRNA levels for CYP1A1 and DNA repair enzymes

Masayoshi Ichiba; Yanping Wang; Jiusong Zhang; Minako Iyadomi; Masafumi Enoki; Katsumaro Tomokuni

The measurement of DNA adducts is a useful indicator for environmental carcinogen exposure monitoring. To clarify the effect of metabolic activation and DNA repair system on the inter-individual variation of DNA adduct levels, aromatic DNA adducts and mRNA expression of metabolic and repair enzymes were measured in 43 human lymphocytes. Aromatic DNA adducts were measured by the nuclease P1 postlabelling method. The metabolic activation enzyme; cytochrome P4501A1 (CYPIA1), and the repair enzyme; excision repair cross complimenting gene (ERCC1), and the xeroderma pigmentosum C group cell gene (XPCC), mRNA expression were measured by the reverse transcription-PCR method. The mean adduct levels were 1.01 ± 0.49 in 43 subjects. There was a positive correlation between DNA adducts and CYP1A1 mRNA (r = 0.33, p = 0.12). DNA adduct levels had a positive correlation with ERCC1 (r = 0.35, p = 0.03) and a negative correlation with XPCC mRNA levels (r = –0.28, p = 0.07). We found Brinkman index, CYP1A1 genotypes, CYP1A1 mRNA and XPCC mRNA as a predictor for log DNA adduct levels in multivariate analysis. Metabolic activation and the repair system may explain the inter-individual variation of DNA adducts in lymphocytes.


Biomarkers | 2001

Lymphocyte DNA adducts and polymorphism in the DNA repair enzyme XPD

Masayoshi Ichiba; Jiusong Zhang; Chikako Kiyohara; Yoichi Nakanishi; Koichi Takayama; Nobuyuki Hara; Masafumi Enoki; Katsumaro Tomokuni

The effect of genetic polymorphism of DNA repair enzyme on the DNA adduct levels was evaluated in this study. We explored the relationship between polymorphism in the nucleotide excision repair enzyme XPD and DNA adduct levels in lymphocytes. Lymphocyte DNA adducts were measured by a (32.)The effect of genetic polymorphism of DNA repair enzyme on the DNA adduct levels was evaluated in this study. We explored the relationship between polymorphism in the nucleotide excision repair enzyme XPD and DNA adduct levels in lymphocytes. Lymphocyte DNA adducts were measured by a 32


Occupational and Environmental Medicine | 1971

Excretion of organic chlorine compounds in the urine of persons exposed to vapours of trichloroethylene and tetrachloroethylene.

Masana Ogata; Yoshiko Takatsuka; Katsumaro Tomokuni

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Kunio Hara

Teikyo Heisei University

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Guowei Pan

Centers for Disease Control and Prevention

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Ken Takahashi

University of Occupational and Environmental Health Japan

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Chung Gyu Park

Seoul National University

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Daehee Kang

Seoul National University

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